Proposal #: 15-06 NEW

2013 FASEB SCIENCE RESEARCH CONFERENCES ADVISORY COMMITTEE MEETING

TOPIC FOR CONSIDERATION TOPIC NAME: MOLECULAR AND SYSTEMS INTEGRATION OF GENOMIC AND NONGENOMIC STEROID

HORMONE ACTION PREVIOUS TITLE: N/A SUBMITTED BY: Donald DeFranco, University of Pittsburgh, School of Medicine Paul Micevych, University of California – Los Angeles

Nancy Weigel, Baylor College of Medicine Martin Kelly, Oregon Health and Science University Brian Harvey, Royal College of Surgeons in Ireland Ellis Levin, Long Beach VA Medical Center

YEAR REQUESTED FOR

SCHEDULING: 2015

SITE REQUESTS: 1. Big Sky, MT

2. Itasca, IL 3. Snowmass, CO

DATE REQUESTS: 1. August 9-14, 2015

2. August 23-28, 2015 3. September 27 – October 2, 2015

YEAR(S) CONFERENCE

HAS BEEN HELD: N/A

NOTES: To the best of our knowledge, there is not a direct conflict with any other

FASEB SRC or other society or industry meeting.

Dear Colleague, We invite you to submit a proposal for a future FASEB Science Research Conference Series (SRC). Since 1982, FASEB has worked hand-in-hand with scientists to organize conferences for experimental biologists. The Conferences are divided up into small groups, who meet intimately and without distractions to explore new approaches to research areas undergoing rapid scientific change. FASEB supports over 35 SRCs each year. Site preferences for 2015, 2016, and 2017 are Big Sky, MT, Chicago, IL, Saxtons River, VT, Snowmass, CO, Steamboat Springs, CO, Nassau, Bahamas, Keystone, CO, Liverpool, England, Palm Beach, FL Palm Springs, CA, Reno/Las Vegas, NV, and Lisbon, Portugal Site preference selection will be prioritized by site availability, history of conference success and registration fee factors. Additionally, FASEB welcomes new site suggestions that are conducive to conference requirements. Please review the attached information and feel free to contact the SRC Office should you have any questions or need guidance in preparing your proposal. We look forward to welcoming you and your conference into the FASEB Science Research Conferences series. Sincerely, The FASEB SRC Staff: Marcella Jackson, CMP, Director (mjackson@faseb.org) Robin Crawford, CMP, Conference Manager (rcrawford@faseb.org) Kristen Hagy, CMP, Conference Manager (khagy@faseb.org) Trina Eacho, Conference Coordinator (teacho@faseb.org) Clay Pencek, Administrative Assistant (cpencek@faseb.org) Main Number: 301-634-7010

FASEB SRC Proposal Instructions

Attached are the instructions and requirements for submitting a FASEB SRC proposal. Please complete sections 1-6 before submitting your information. Please submit your proposal by September 23, 2013 in order to be considered for the 2015 SRC Series.

Proposals will be reviewed by the FASEB Science Research Conference Advisory Committee in mid November. Shortly thereafter, you will receive a letter with the committee’s decision on your submitted proposal. By the end of January 2014 you will receive a second letter which will indicate the location and date for your conference as well as the name of your assigned Conference Manager. Once your conference is approved, your conference manager will schedule a kick-off conference call to discuss timelines, expectations, instructions on fund raising, and program management to help make your organization process successful.

Section 1: Organizer Responsibilities By submitting a FASEB Science Research Conference proposal for consideration by the FASEB SRC Advisory Committee, the organizer(s) accepts the responsibility for producing a successful conference. These responsibilities include:

1. Anything related to the scientific portion of your conference. You will need to provide the Conference title and topics. The Conference title and topics should be timely and attractive. 2. Organizers must assist in recruiting no less than 100 participants to the conference. 3. All fundraising efforts are the responsibility of the organizers with support and guidance by the FASEB SRC Staff. FASEB will provide $10,000 for each conference to help defray a portion of travel and registration costs for speakers. 4. Organizers are responsible for contacting all speakers and session chairs and inviting and confirming their participation. Speakers should be informed that their expenses will be reimbursed after the conference and only to the extent that funds are available. We recommend you do not commitment to a speaker a specific amount of funds prior to the Conference. (Note: Invited speakers and session chairs are required to remain at the Conference for a minimum of three full days and three full nights in order to be eligible for reimbursement of any Conference related expenses.) 5. Organizers must include a “Meet the Expert” session in the program. This session is aimed at encouraging the younger investigators an opportunity to network with the more established and senior PIs in your field. This session can be scheduled during meals or at poster sessions. 6. Organizers must provide conference agenda for posting online. 7. Organizers must provide a final conference agenda. It is the organizers’ responsibility to provide the speaker abstracts (in presentation order), poster abstracts, and a poster listing of the submitted abstracts. The Conference Manager will prepare the cover for the program, the participant list and have the final packet of materials reproduced and shipped to the venue. 8. Organizers must provide conference agenda for posting online. 9. Organizers will participate in periodic discussions with their assigned Conference Manager. By doing so, this will eliminate any miscommunication or understanding of the policies and procedures that will needed to be followed.

Section 2: Conference Title & Organizer Information: Please insert the title of the Conference as you would like it to be advertised in future publications. List the organizing committee below and complete contact information and attach a brief CVs (maximum 3 pages) in NIH format for each. TITLE OF CONFERENCE: # of EXPECTED ATTENDEES: Preferred Primary Point of Contact for Proposal Questions: Name: Full Address: Telephone #: Email Address: Science Categories (select up to 3)

1) 2) 3) (see Attachment A - for marketing and audience generation purposes) Organizing Committee: Organizer Chair: __________________________ __Title: ____________________ Affiliation: ___________________________________________________________________ Full Address: ________________________________________________________________ ___________________________________________________________________________ Phone: _______________________ Email: ________________________________________ Organizer Co-Chair __________________________________Title: ____________________ Affiliation: ___________________________________________________________________ Full Address: ________________________________________________________________ ___________________________________________________________________________ Phone: _______________________ Email: ________________________________________ Committee member: __________________________________Title: ____________________ Affiliation: ___________________________________________________________________ Full Address: ________________________________________________________________ ___________________________________________________________________________ Phone: _______________________ Email: ________________________________________ Committee member: __________________________________Title: ____________________ Affiliation: ___________________________________________________________________ Full Address: ________________________________________________________________ ___________________________________________________________________________ Phone: _______________________ Email: ________________________________________

Committee member: __________________________________Title: ____________________ Affiliation: ___________________________________________________________________ Full Address: ________________________________________________________________ ___________________________________________________________________________ Phone: _______________________ Email: ________________________________________ Committee member: __________________________________Title: ____________________ Affiliation: ___________________________________________________________________ Full Address: ________________________________________________________________ ___________________________________________________________________________ Phone: _______________________ Email: ________________________________________

Section 3: Program Submission Requirements & Outline:

Please insert program details in day order as requested below. Session titles should be listed with session chairs and affiliations. Indicate the proposed tentative talk titles within each session and list up to at least 4 speakers per session (not including short talks selected from submitted abstracts). Please remember to also include the required “Meet the Expert” session. The FASEB SRC Advisory Committee requires all session chairs to be confirmed before the submission of the application. Be sure to indicate with a "C" if the session chair is confirmed, indicate with a “CS” if the speaker is confirmed, indicate with a "W" which session chairs and speakers are women, indicate with an "M" which session chairs and speakers are of a minority group and indicate with the word “NEW” which session chairs and speakers are new to the program. (Note: The committee defines new speakers as one that has NOT spoken at the last two (2) Conferences.) Overview of Program Flow # of Days: # of Sessions per day: # of Speaker per day: # of Session chairs per day: # of Breakouts per day: # of Abstracts per day: SUNDAY To include: Conference Registration 4 p.m. – 9 p.m., FASEB SRC Welcome Reception 5 p.m. – 6 p.m., Dinner 6 p.m. – 7 p.m. Title of Session: ______________________________________________________________ Session Chair & Affiliation:_____________________________________________________ Additional Session Titles (if applicable): Title of Session: ______________________________________________________________ Session Chair & Affiliation:______________________________________________________ Title of Session: ______________________________________________________________ Session Chair & Affiliation:______________________________________________________

Speaker 1: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 2: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 3: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 4: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Title of Session: ______________________________________________________________ Session Chair & Affiliation:_____________________________________________________ Speaker 1: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 2: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 3: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 4: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Number of short talks selected from abstracts: _____ MONDAY To include: Group photo during morning break Title of Session: ______________________________________________________________ Session Chair & Affiliation:_____________________________________________________ Additional Session Titles (if applicable): Title of Session: ______________________________________________________________ Session Chair & Affiliation:______________________________________________________ Title of Session: ______________________________________________________________ Session Chair & Affiliation:______________________________________________________

Speaker 1: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 2: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 3: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 4: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Title of Session: ______________________________________________________________ Session Chair & Affiliation:_____________________________________________________ Speaker 1: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 2: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 3: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 4: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Number of short talks selected from abstracts: _____ TUESDAY Title of Session: ______________________________________________________________ Session Chair & Affiliation:______________________________________________________ Additional Session Titles (if applicable): Title of Session: ______________________________________________________________ Session Chair & Affiliation:______________________________________________________ Title of Session: ______________________________________________________________ Session Chair & Affiliation:______________________________________________________ Speaker 1: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________

Speaker 2: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 3: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 4: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Title of Session: ______________________________________________________________ Session Chair & Affiliation:_____________________________________________________ Speaker 1: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 2: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 3: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 4: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Number of short talks selected from abstracts: _____ WEDNESDAY Title of Session: ______________________________________________________________ Session Chair & Affiliation:______________________________________________________ Additional Session Titles (if applicable): Title of Session: ______________________________________________________________ Session Chair & Affiliation:______________________________________________________ Title of Session: ______________________________________________________________ Session Chair & Affiliation:______________________________________________________ Speaker 1: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 2: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________

Speaker 3: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 4: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Title of Session: ______________________________________________________________ Session Chair & Affiliation:_____________________________________________________ Speaker 1: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 2: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 3: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 4: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Number of short talks selected from abstracts: _____ THURSDAY To include: Group activity 1 p.m. – 5 p.m. (optional) Title of Session: ______________________________________________________________ Session Chair & Affiliation:______________________________________________________ Additional Session Titles (if applicable): Title of Session: ______________________________________________________________ Session Chair & Affiliation:______________________________________________________ Title of Session: ______________________________________________________________ Session Chair & Affiliation:______________________________________________________ Speaker 1: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 2: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________

Speaker 3: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 4: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Title of Session: ______________________________________________________________ Session Chair & Affiliation:_____________________________________________________ Speaker 1: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 2: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 3: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 4: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Number of short talks selected from abstracts: _____ Possible Group Activity:________________________________________________________ FRIDAY Option 1: Half-day session, departures at 12 p.m. w/box lunch Option 2: Breakfast, departures at 9 a.m. Title of Session: ______________________________________________________________ Session Chair & Affiliation:_____________________________________________________ Additional Session Titles (if applicable): Title of Session: ______________________________________________________________ Session Chair & Affiliation:______________________________________________________ Title of Session: ______________________________________________________________ Session Chair & Affiliation:______________________________________________________ Speaker 1: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 2: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________

Speaker 3: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 4: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Title of Session: ______________________________________________________________ Session Chair & Affiliation:_____________________________________________________ Speaker 1: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 2: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 3: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Speaker 4: __________________________________________________________________ Affiliation: ___________________________________________________________________ Tentative Title of Talk: _________________________________________________________ Number of short talks selected from abstracts: _____

End of Conference

Section 4: Content Assessment: Please complete the grid below which will assist the FASEB SRC Advisory Committee in assessing the requirements of the proposal. Positive reviews are given to proposals with confirmation of session chairs and invited speakers, new speakers to the program, a good representation of women, and a sufficient number of short talks from junior level investigators. Indicate the number of session chairs that have confirmed their participation: Indicated the number of women included with the entire program: Indicate the number of session chairs/speakers of a minority group: Indicate the number of new speakers to the Conference: Indicate the number of speakers that have confirmed their participation in the Conference: Indicated the number of talks set aside for junior level investigators to present their work: Indicated the number of poster sessions that will be organized: Please provide a brief description of the how the poster sessions will be organized: Indicate (if known) if there is a potential of a conflict with any other FASEB SRC or any other society or industry meeting. If yes, please explain the conflict in detail.

Section 5: Scheduling & Location Preferences:

Select three (3) choices of dates that you wish to hold the Conference. Define the pattern flow, start date, and end date of your Conference Week 1: ___________________ Week 2: ___________________ Week 3: _______________ Select at least three (3) cities/venues for consideration. Venue #1 should be the most preferred. (Note: We will do our best to give you your first choice but it cannot be guaranteed). Please mark the type of facility you would like to host the program. Hotel Conference Center University, Academic Setting (summer only)

Cities/venues Preference 1 2 3 1 2 3 1 2 3

Big Sky, MT TRADITIONAL VENUES:

Chicago, IL Saxtons River, VT (University setting) Snowmass, CO Steamboat Springs, CO Nassau, Bahamas (passport required, government funding may be limited)

Keystone, CO NEW:

Liverpool, England (passport required, government funding may be limited) Palm Beach, FL Palm Springs, CA Reno/Las Vegas, NV Locations are contingent upon group interest. Every effort will be given to the Organizer’s choice of venue and date choice. Due to limited availability and scheduling site and date preferences are not guaranteed. For each conference year, a minimum of four (4) conference proposals should have interest in a potential venue in order for that venue to be used as a conference location.

Section 6: Justification:

The SRC Advisory Committee requires all proposals to include answers to the following twelve (12) questions. In a separate Microsoft Word document, answer each individual question accordingly. Once completed, name the document the title of your Conference and attach this file to your email when submitting the final proposal. 1. Why is this topic of high current interest to the scientific community? 2. Is this a rapidly growing field? 3. Have there been previous Conferences of this topic? If so, where and when were the Conferences held? How many participants attended? (Additionally, consider whether or not another similar Conference /meeting is scheduled that might cause a conflict). 4. How many participants do you expect to attend the Conference? 5. What percentage of women have participated in this Conference in the past (if it has been previously held)? 6. How will you recruit young investigators to attend and participate in the Conference? 7. How will you recruit and select new speakers? 8. Who will attend this conference? (Provide specifics)

9. From what sources and resources will you use to solicit funds for the Conference? (Provide specifics). 10. Where will the Conference be advertised? What types of media will be used to advertise your Conference? (Provide specifics). 11. What societies and disciplines will you attract to attend the conference? (Provide specifics) 12. Are you planning on submitting a similar application to another organization for additional funding and sponsorship? If yes, please clarify.

Section 7: Submitting Your Proposal: Please read the directions below for submitting your proposal. Feel free to contact the SRC Office should you have any questions or need guidance in submitting your proposal. Instructions for submitting your proposal: 1. Print or save a copy of this form for your own records. 2. Email Robin Crawford, CMP at rcrawford@faseb.org. 3. Enter the title of your Conference and the year of the conference in the subject line. 4. Attach the following items to your e-mail:

• The file with the answers to the nine questions in Section 6: Justification • CVs (in NIH Format) for all Organizers and Co-Organizers (maximum of 3 pages).

Thank you in advance for your proposal submission! We look forward to helping you plan a successful Conference.

For more information, please contact:

Marcella Jackson, Director, Office of Meetings and Conferences 301-634-7010, mjackson@faseb.org Robin Crawford, Conference Manager, FASEB Science Research Conferences 301-634-7093, rcrawford@faseb.org Kristen Hagy, CMP, Conference Manager, FASEB Science Research Conferences 301-634-7094, khagy@faseb.org Trina Eacho, Conference Coordinator, FASEB Science Research Conferences 301-634-7206, teacho@faseb.org Clay Pencek, Administrative Assistant, FASEB Science Research Conferences 301-634-7018, cpencek@faseb.org

Biology Categories

Aerobiology – the study of airborne organic particles Agriculture – the study of producing crops from the land, with an emphasis on practical applications Anatomy – the study of form and function, in plants, animals, and other organisms, or specifically in humans Arachnology – the study of arachnids Astrobiology – the study of evolution, distribution, and future of life in the universe— also known as exobiology, exopaleontology, and bioastronomy Biochemistry – the study of the chemical reactions required for life to exist and function, usually a focus on the cellular level Bioengineering – the study of biology through the means of engineering with an emphasis on applied knowledge and especially related to biotechnology Biogeography – the study of the distribution of species spatially and temporally Bioinformatics – the use of information technology for the study, collection, and storage of genomic and other biological data Biomathematics (or Mathematical biology) – the quantitative or mathematical study of biological processes, with an emphasis on modeling Biomechanics – often considered a branch of medicine, the study of the mechanics of living beings, with an emphasis on applied use through prosthetics or orthotics Biomedical research – the study of the human body in health and disease Biophysics – the study of biological processes through physics, by applying the theories and methods traditionally used in the physical sciences Biotechnology – a new and sometimes controversial branch of biology that studies the manipulation of living matter, including genetic modification and synthetic biology Building biology – the study of the indoor living environment Botany – the study of plants Cell biology – the study of the cell as a complete unit, and the molecular and chemical interactions that occur within a living cell Conservation biology – the study of the preservation, protection, or restoration of the natural environment, natural ecosystems, vegetation, and wildlife Cryobiology – the study of the effects of lower than normally preferred temperatures on living beings Developmental biology – the study of the processes through which an organism forms, from zygote to full structure Ecology – the study of the interactions of living organisms with one another and with the non-living elements of their environment

Embryology – the study of the development of embryo (from fecundation to birth) Entomology – the study of insects Environmental biology – the study of the natural world, as a whole or in a particular area, especially as affected by human activity Epidemiology – a major component of public health research, studying factors affecting the health of populations Epigenetics – the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence Ethology – the study of animal behavior Evolutionary biology – the study of the origin and descent of species over time Genetics – the study of genes and heredity Hematology ( also known as Haematology ) - the study of blood and blood - forming organs. Herpetology – the study of reptiles and amphibians Histology – the study of cells and tissues, a microscopic branch of anatomy Ichthyology – the study of fish Integrative biology – the study of whole organisms Limnology – the study of inland waters Mammalogy – the study of mammals Marine biology (or Biological oceanography) – the study of ocean ecosystems, plants, animals, and other living beings Microbiology – the study of microscopic organisms (microorganisms) and their interactions with other living things Molecular biology – the study of biology and biological functions at the molecular level, some cross over with biochemistry Mycology – the study of fungi Neurobiology – the study of the nervous system, including anatomy, physiology and pathology Oncology – the study of cancer processes, including virus or mutation oncogenesis, angiogenesis and tissues remoldings Ornithology – the study of birds Population biology – the study of groups of conspecific organisms, including o Population ecology – the study of how population dynamics and extinction o Population genetics – the study of changes in gene frequencies in populations of organisms Paleontology – the study of fossils and sometimes geographic evidence of prehistoric life Pathobiology or pathology – the study of diseases, and the causes, processes, nature, and development of disease Parasitology – the study of parasites and parasitism Pharmacology – the study and practical application of preparation, use, and effects of drugs and synthetic medicines Physiology – the study of the functioning of living organisms and the organs and parts of living organisms

Phytopathology – the study of plant diseases (also called Plant Pathology) Psychobiology – the study of the biological bases of psychology Sociobiology – the study of the biological bases of sociology Structural biology – a branch of molecular biology, biochemistry, and biophysics concerned with the molecular structure of biological macromolecules Synthetic Biology- research integrating biology and engineering; construction of biological functions not found in nature Virology – the study of viruses and some other virus-like agents Zoology – the study of animals, including classification, physiology, development, and behavior (branches include: Entomology, Ethology, Herpetology, Ichthyology, Mammalogy, and Ornithology)

APPLICATION FOR FASEB 20105 SUMMER CONFERENCE Molecular and Systems Integration of Nongenomic and Genomic Steroid Hormone Signaling Conference Chair Donald B. DeFranco, Ph.D. Professor of Pharmacology & Chemical Biology University Of Pittsburgh School of Medicine 7041 Biomedical Sciences Tower 3 3501 Fifth Avenue Pittsburgh, PA 15260 Telephone: 412-624-4259 Conference Co-Chairs Nancy Weigel, Ph.D. (Baylor College of Medicine) Paul Micevych, Ph.D (University of California, Los Angeles) Organizing Committee Ellis Levin, M.D. (VA Medical Center, Long Beach, CA) Stephen R. Hammes, M.D./Ph.D. (University of Rochester School of Medicine) Martin Kelly, Ph.D. (Oregon Health Sciences Center University) Brian Harvey, Ph.D. (Royal College of Surgeons, Ireland)

Section 6: Justification 1. Why is this topic of high current interest to the scientific community? There is a growing interest and more in depth understanding of the molecular basis for various intracellular and intercellular signaling pathways that impact hormone action. Specifically, nuclear hormone receptors that trigger short and long term changes in cellular physiology through the regulation of gene expression, also mobilize cytoplasmic signaling pathways through rapid actions initiated by plasma membrane bound receptors. However, nuclear hormone receptors do not act in isolation to modulate cytoplasmic and nuclear signaling pathways but rely on complex networks of interacting molecules to integrate rapid cytoplasmic and more long-term genomic actions to generate an appropriate response. Furthermore, cellular, tissue and organ “networks” act in concert to elicit a systems-wide response that insures that the whole organism responds to changes in physiological states communicated by circulating hormones. This conference will highlight the mechanisms whereby cell signaling pathways involving steroid receptors are integrated. The topics cover many organ systems and signaling pathways, thus bringing together investigators who usually attend either more organ- or receptor-focused meetings. In the past, the breadth of this meeting led to significant cross-fertilization of ideas and in depth discussions. This dialogue creates significant opportunities for translation into important new medical therapies. Prior attendees indicate this to be a major strength, and we will continue to emphasize cross-fertilization for the 2015 meeting. This meeting, particularly the current iteration proposed in the 2015 roster of speakers has the potential to create a unique opportunity for multi-disciplinary exchange. 2. Is this a rapidly growing field? Over the years, the scientific community has recognized the complex nature of nuclear hormone receptor signaling; for example, a pubmed search of “nongenomic” and “steroid” identifies over 1000 publications, most from work performed in the past 10 years. A search of “nongenomic” and “nuclear receptor” identified 712 papers, 10% of which were published in the last year alone. With the exploitation of new technologies in transgenic mice generation and gene ablation, the impact of nuclear hormone receptor signaling in heretofore unrecognized organ systems physiology has emerged as evidenced by the recent discovery of the important role for the glucocorticoid receptor in heart development and function. The topic of “nongenomic” or rapid, non-classical action of nuclear hormone receptors now receives substantial coverage in large international conferences such as the Endocrine Society meeting and the Society for Neuroscience meeting. 3. Have there been previous Conferences of this topic? If so, where and when were the Conferences held? How many participants attended? (Additionally, consider whether or not another similar Conference /meeting is scheduled that might cause a conflict). FASEB has now sponsored eight summer conferences on “nongenomic and genomic steroid hormone signaling” from 2000 to 2012. The number of participants has ranged from 65 – 85. All conferences were held in Tucson or Carefree until the 2010 meeting, which was held in Snowmass. Within the movement of the National Endocrine Society Meeting from June to March beginning in 2015, this proposed FASEB SRC will be relieved of a major competing conference. In addition, requested dates for this FASEB

SRC (i.e. mid-late August or mid September) are well separated from two other small conferences (i.e. Gordon Summer Research Conference on Steroid Hormones and Cancer- late July; EMBO Nuclear Receptor conference-early September) that would have limited overlap with some content proposed in this FASEB SRC. 4. How many participants do you expect to attend the Conference? At the recent 8th International Conference on Rapid Responses to Steroid Hormones (RRSH), a formal plan was agreed upon by the RRSH Steering Committee to merge the RRSH conference and FASEB Integration of Genomic and Nongenomc Nuclear Hormone Receptor conference in 2017. 2015 will be a transition year for this joint FASEB/RRSH venture since the 9th annual RRSH conference has already been scheduled for late Spring in 2015 (Taipei, Taiwan). Nonetheless the 2015 FASEB conference will benefit from the inclusion of three Steering Committee members from the RRSH group (Kelly, Harvey, Levin) on our Advisory Committee and the increased visibility and attractiveness of both conferences given the merger of these two groups. Importantly, a number of speakers to be invited to the 2015 FASEB conference will be selected from speakers at past RRSH meetings, most of whom have not participated in recent FASEB nongenomic nuclear receptor conferences. Furthermore, we expect to attract a number of international attendees in the field of rapid steroid hormone action. We fully expect the merger of FASEB/RRSH conferences to increase attendance at the FASEB conference even in the 2015 transition year. There are additional factors that we anticipate will lead to increased attendance at the 2015 and future FASEB meetings on “nongenomic and genomic steroid hormone action” in addition to the merger of RRSH and FASEB nongenomic groups. These are bulleted below.

• The FASEB nongenomic conference will now be held in odd years and therefore out-of-synch with the very popular Keystone Nuclear Receptor conferences, which are held in late spring in even numbered years.

• Beginning in 2015, the Endocrine Society Meeting shifts from the position it’s

held for many years in (i.e. mid – late June) to late March/early April. This large gap between the Endocrine Society meeting and proposed FASEB meetings in late summer enhances the chances of obtaining speakers and attendees who are consistent supporters of the Endocrine Society Meeting.

5. What percentage of women has participated in this Conference in the past? The percentage of women attending our previous meetings has always been about 35-40%. We have maintained this high degree of gender equity in this year’s proposed conference that includes 12/33 (36%) women and 2 underrepresented minorities. We will also maintain gender equity as far as possible in selecting short talk speakers from the abstracts. The 2012 conference on this topic included 17/33 women and 2 underrepresented minorities. 6. How will you recruit young investigators to attend and participate in the Conference? As evidenced by the feedback provided by junior attendees, we have had great success with our trainees in previous meeting, mainly due to the open and informal interactions that take place. After the last two conferences, the organizers received personal emails

from nearly every trainee participant complimenting us on the meeting and thanking us for including them. We have made a priority of providing travel grants to every single individual that presented an abstract at the 2008, 2010 and 2012 meetings, and we hope to do the same in 2015. We will also choose 8 of the best abstracts to give short oral presentations and give 4 trainees with poster presentations to give a very brief preview of their posters at the end of the each morning sessions. This “speed dating” approach was used successfully at the most recent Endocrine Society meeting and will provide another 16 trainees with some exposure to the entire group. We anticipate that the increased opportunities to speak and advertising our past success in raising travel money will markedly increase the number of abstract submissions in 2015. Other plans to improve recruitment include: 1) Invited speakers are asked to bring at least one junior investigator from their laboratories and one colleague from their institution to attend the meeting. 2) We will continue to work with the Endocrine Society, who has been a strong advocate of this meeting and of trainee development, to improve visibility of the meeting. This includes advertising in the Endocrine Society journals and at the annual Endocrine Society meeting. 3) Through Drs. Kelly and Levin, we will work with the Neuroscience, Cancer Research and Cardiovascular organizations to increase our visibility. 7. How will you recruit and select new speakers? Members of the conference Organizing Committee and co-Chairs have provided thoughtful suggestions for new speakers. We polled the most successful speakers at the last meeting and other internationally established experts in regard to speaker selection. The re-orientation of this year’s meeting met with significant interest on the part of researchers from both the genomic and non-genomic steroid receptor action fields. We have also made a special effort to include junior faculty of excellent credentials on our speaker roster. Given the wide range of expertise of the conference organizers, we were able to devise a conference with 22/33 (67%) new speakers as well as 7/33 international speakers from 6 countries. 8. Who will attend this conference? (Provide specifics). As in previous years, this conference will attract a diverse group of scientists with interests in steroid hormone action in physiological (i.e. epithelial cell biology, energy homeostasis, cardiovascular function, brain function) and pathophysiological (i.e. cancer, metabolic syndrome) states. This year we have added a new session devoted entirely to the emerging field of epigenetics including speakers who will discuss the impact of environmental agents on the development of steroid hormone responses. With the increased exposure to the international RRSH group, we expect to attract a larger number of international attendees. The RRSH group has held 8 previous conferences in different countries throughout the world (e.g. Greece, Taiwan, in recent years). The 2012 FASEB conference on this topic included 4 international speakers. This proposed 2015 conference includes 7 international speakers. 9. Sources from which financial support will be sought: We have been very successful, indeed exemplary at fundraising for this conference in the past. In 2008 and 2010 we completely funded every invited US speaker, and provided travel awards for every other presenter. The 2012 conference received $59,000 of support from diverse sources such as NIH ($5,000. R13 grant in 2012 from NIDDK), NSF ($22,000), Ordway Institute ($4,000.), Pfizer Pharmaceuticals and The Endocrine Society ($2,500.). As in previous

years, we will solicit funds from both public and private sources. We have already obtained a verbal and written commitment for $10,000 from the Ordway Institute for the 2015 meeting. A list of funding assignments has been developed that currently includes the following:

NIH Donald DeFranco NSF Martin Kelly The Physiological Society Brian Harvey Endocrine Society Donald DeFranco Ordway Institute Pepper Davis Genentech Martin Kelly Pfizer Joyce Slingerland Lilly Stephen Hammmes Novartis Joyce Slingerland

10. Media to be used for advertising: We will advertise in FASEB Journal, Molecular Endocrinology, Endocrinology, Thyroid, Cancer Research, Cancer Cell and Science. We will also advertise by word of mouth, email, and through announcements at the Annual Meetings for the aforementioned societies. 11. What societies and disciplines will you attract to attend the conference? As mentioned, the broad nature of this growing discipline makes it of interest to many fields, including neurobiology, endocrinology, oncology, immunology, and cardiology. The societies from which we will draw attendees include but are not limited to: Endocrine Society, American Thyroid Association, American Societies of Cell Biology and Biochemistry, the American Heart Association, Society for Neuroscience, American Association for Cancer Research and the Physiological Society. Importantly, as mentioned earlier, the FASEB nongenomic conference will now be the “go-to” conference for international members of the Rapid Responses to Steroid Hormones (RRSH) group. The RRSH group has run 8 well-funded and well-attended international conferences and will aid in the 2015 and all subsequent FASEB conferences. 12. Are you planning on submitting a similar application to another organization for additional funding and sponsorship? As in past years with this conference, we will submit applications for support to the NIH (NIDDK), NSF, Endocrine Society and The Physiological Society. Industry support will also be solicited.

PHS 398/2590 (Rev. 11/07) Page Biographical Sketch Format Page

Program Director/Principal Investigator (Last, First, Middle): DeFranco, Donald Benedict

BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors in the order listed

on Form Page 2.

NAME Donald B. DeFranco

POSITION TITLE Professor

eRA COMMONS USER NAME (credential, e.g., agency login) ddefranco

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as INSTITUTION AND LOCATION

DEGREE (if

applicable) YEAR(s) FIELD OF STUDY

Temple University, Philadelphia, PA B.A. 1972-1976 Biology Yale University, New Haven, CT Ph.D. 1977-1981 Molecular Biophysics &

Biochemistry University of California, San Francisco, CA Postdoc 1982-1985 Biochemistry

A. Personal Statement

My laboratory has spent nearly 25 years examining the glucocorticoid receptor function focusing predominantly on the mechanisms of glucocorticoid receptor transactivation, interaction with coactivators, subcellular and subnuclear trafficking, interactions with molecular chaperones and processing. In many of the publications resulting from these studies, graduate students and young postdoctoral trainees were first authors. I have trained 22 graduate students (Including 3 MD/PhD students) and 11 postdoctoral researchers. There are currently 3 graduate students and 3 postdoctoral researchers working in my laboratory. Over the years we have utilized various experimental model systems to provide novel mechanistic insights into receptor action. Some of our studies are utilized neuronal cell systems and in particular, we were one of the first to provide direct demonstration of glucocorticoid receptor tethering to a DNA-bound transcription factor of the homeodomain family (i.e. Oct-1) utilizing a cell line of hypothalamic origin. Furthermore, using cells of hippocampal origin we provided one of the first demonstrations of developmentally regulated receptor degradation that is likely to be influenced by a receptor co-chaperone (e.g. CHIP). We have furthermore utilized state of the art molecular approaches (e.g. chromatin immunoprecipitation) to provide insights into receptor interactions with unique coregulator proteins (i.e. Hic-5) on chromatin. In the past few years we have initiated a collaboration with Dr. Paula Monaghan-Nichols, a developmental neurobiologist with expertise in the role of select transcription factors in neural stem cell proliferation, cell cycle transit and differentiation, to expand our analysis of glucocorticoid receptor function to an area of clinical relevance. Clinical studies of postnatal and antenatal glucocorticoid administration and both in-vivo and in-vitro animal studies suggest that detrimental effects of these hormones on neural function in adults and juveniles may be caused by alterations in the proliferation and differentiation of embryonic neural stem cells. Specifically, the administration of glucocorticoids has been found to decrease the in-vitro and in vivo proliferative capacity of embryonic neural stem cells via cell cycle protein dependent processes and also alter the pattern and rate of neural stem cell differentiation.

B. Positions and Honors

Positions and Employment 1977-1981 Graduate Research Assistant, Laboratory of Dr. Dieter Söll, Department of Molecular Biophysics

and Biochemistry, Yale University, New Haven, CT 1982-1985 Postdoctoral Fellow, Laboratory of Dr. Keith Yamamoto, Department of Biochemistry and

Biophysics, University of California, San Francisco, CA 1985-1991 Assistant Professor, Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA

PHS 398/2590 (Rev. 11/07) Page 2 Biographical Sketch Format Page

1991- 1996 Associate Professor, Department of Biological Sciences, University of Pittsburgh 1996 – 2000 Professor, Department of Biological Sciences, University of Pittsburgh 1997 - Professor, Department of Neuroscience, University of Pittsburgh (Secondary Appointment) 1998 Acting Chairman, Department of Biological Sciences, University of Pittsburgh 2000 - Professor, Department of Pharmacology, University of Pittsburgh School of Medicine Other Experience and Professional Memberships 1995- 2008 Editorial Board (1995-2003), Associate Editor (2004-2008), Molecular Endocrinology 2009 - Editor-in-Chief, Molecular Endocrinology 1996- 2001 Editorial Board, Journal of Biological Chemistry (1996-2001), Neuroendocrinology (1997-1999) 2001- 2003 Director, Molecular Biology Section of “Course in Neurobiology”, Marine Biological Laboratory,

Woods Hole, MA Honors 1976 Summa cum laude, Honors in Biology, Phi Beta Kappa, N.D. Lane Science Prize 1982-1983 Damon Runyon-Walter Winchell Postdoctoral Fellowship 1986-1989 Basil O'Connor Starter Scholar Award, March of Dimes Foundation 1991-1996 Research Career Development Award, National Cancer Institute Federal Government Public Advisory Committee Service 1992-1998 Endocrinology Study Section, ad-hoc (1992-1994), full member (1994-1998) 1993-2005 National Institutes of Health Special Emphasis Panels or Site Visits

1. NIDDK Program Project on "Mechanism of Growth Control by Steroids", UTHSC, Galveston, TX (11/93, 03/95), 2. NINDS Special Study Section, “Parkin Protein and Parkinson’s Disease” (11/00), 3. NINDS Special Mock Study Section on “Hypothermia and Neuroprotection”, University of Alaska-Fairbanks (09/02), 4. Biochemical and Endocrinology Sciences Study Section Special Emphasis Panel on “Reproductive Sciences” (03/03, 11/03), 5. NCI Program Project on “Mechanisms of Prostate Cancer”, University of Virginia (06/03, 02/04), 6. NIA Special Emphasis Panel on “Reproductive Hormones and the Brain” (11/05)

2007 Molecular and Cellular Endocrinology Study Section, ad-hoc member 2007- Biomedical Research and Training (BRT-A) Study Section, full member

C. Selected peer-reviewed publications Most Relevant to the current application (Graduate Students as 1st Authors)

1. Levinthal DJ, DeFranco DB. (2005) Reversible oxidation of ERK-directed protein phosphatases drives oxidative toxicity in neurons. J. Biol Chem. 280, 5875-5883. 2. Heitzer M.D. and DeFranco D.B. (2006) Regulation of androgen induced KGF gene transcription in prostate stromal cells by a cell type-restricted androgen receptor coactivator, Hic-5/ARA55. Cancer Res. 66, 7326-7333. PMID: 16849583 3. Ho Y*, Samarasinghe R*, Knoch ME, Lewis M, Aizenman E, DeFranco DB. (2008) Selective inhibition of MAPK phosphatases by zinc accounts for ERK1/2-dependent oxidative neuronal cell death. Molecular Pharmacology 74, 1141-1151. (*co-first authors) PMCID: PMC2575064 4. Samarasinghe RA, Di Maio R, Volonte D, Galbiati, F, Lewis M, Romero G, DeFranco DB (2011). Non-genomic glucocorticoid receptor action regulates gap junction intercellular communication and neural progenitor cell proliferation. Proc. Natl. Acad. Sci. USA 108, 16657-16662. PMID: 21930911 5. Grubisha, MJ, Cifuentes ME, Hammes, S, DeFranco DB (2012). A local paracrine and endocrine network involving TGFβ, Cox-2, ROS and estrogen receptor beta impacts reactive stromal cell regulation of prostate cancer cell motility. Mol. Endocrinol. 26, 940-954. PMCID: PMC3355541

PHS 398/2590 (Rev. 11/07) Page 3 Biographical Sketch Format Page

Additional recent publications of importance to the field (in chronological order) (selected from 102 publications) 1. Cummings, C.J., Mancini, M.A., Antalffy, B., DeFranco, D.B., Orr, H.T., and Zoghbi, H.Y. (1998). Chaperone suppression of ataxin-1 aggregation and altered subcellular proteosome localization imply misfolding in SCA1. Nature Genet. 19, 148-154. PMID: 9620770 2. Xiao, N., Callaway, C.W., Lipinski, C.A., Hicks, S.D., and DeFranco, D.B. (1999). Geldanamycin provides post-treatment protection against glutamate-induced oxidative toxicity in a mouse hippocampal cell line. J. Neurochem., 72, 95-101. PMID: 988605 3. Chandran, U.R., Warren, B.S, Baumann, C.T., Hager, G.L., and DeFranco D.B. (1999). The glucocorticoid receptor is tethered to DNA-bound Oct-1 at the mouse GnRH distal negative glucocorticoid response element. J. Biol. Chem. 274, 2372-2378. PMID: 9891005 4. Liu, J., and DeFranco, D.B. (1999). Chromatin recycling of glucocorticoid receptors: Implications for multiple roles of heat shock protein 90. Mol. Endocrinol.13, 355-365. PMID: 10076993 5. Stanciu, M., Wang, Y., Kentor, R., Burke, N., Watkins, S., Klann, E. Johnson, J. and DeFranco, D.B. (2000). Persistent activation of ERKs is a late event that contributes to glutamate-induced oxidative toxicity in a neuronal cell line and primary cortical neuron cultures. J. Biol. Chem. 275, 12200-12206. PMID: 10766856 6. Jiang H, Nucifora, F., Ross, C.A., and DeFranco D.B. (2003). Cell death triggered by polyglutamine-expanded huntingtin in a neuronal cell line is associated with degradation of CREB-binding protein. Human Mol. Genet. 12, 1-12. PMID: 12490527 7. Kasai, M, Guerrero-Santoro, J, Friedman, R, Leman ES. Getzenberg, RH, and DeFranco D.B. (2003). The group 3 LIM domain protein paxillin potentiates androgen receptor transactivation in prostate cancer cell lines. Cancer Research, 63, 4927-4935. PMID: 12941817 8. Elbi C, Romero G., Walker D., Sullivan W., Toft, D., Hager G.L. and DeFranco D.B. (2004). Molecular chaperones function as nuclear mobility factors for steroid receptors. PNAS, USA, 101, 2876-2881. PMID: 14978266 9. Heitzer MD, DeFranco DB. (2006) Mechanism of action of Hic-5/ARA55, a LIM domain-containing nuclear receptor coactivator. Mol. Endocrinol., 20, 56-64. 10. Ho Y, Logue E, Callaway CW, DeFranco DB. (2007) Different mechanisms account for ERK activation in distinct brain regions following global ischemia and reperfusion. Neuroscience 145, 248-255. PMID: 17207579 D. Research Support

ACTIVE 1. “Predoctoral Training in Pharmacological Sciences” Principal Investigator: Donald B. DeFranco, Ph.D. Agency: NIH/NIGMS Type: T32 (GM08424, Years 11-15) Period 07/01/05-06/30/10 The purpose of this Predoctoral Training Program is to provide a broad education in areas relevant to the pharmacological sciences and to train students in the techniques, strategies and philosophy of modern biological research.

2. “The Chromatin Landscape of Fetal Hypothalamic Stem Cells” Principal Investigator: Donald B. DeFranco, Ph.D. Agency: NIH/NIDDK Type: U24 (DK097746, Year 1): Period 09/17/12 – 08/31/14 The specific aims of this application are: 1) To use global DNase I hypersensitivity (DHS) analysis of fetal HT NSPCs to determine whether GC exposure leads to sex-specific, transient or permanent alterations in chromatin landscape. Global DHS analysis will be performed with fetal HT NSPC cultures derived from male and female embryos to reveal sex-specific differences in GC action. We will also examine NSPC cultures of increasing passages (e.g. P1 vs. P3) during which stem and progenitor cells become progressively lineage restricted as different populations of HT neurons are being specified. 2) To use ChIP-Seq and gene expression microarrays to identify genomic GR occupancy and regulated transcripts, respectively, in fetal HT NSPCs of different sexes and stages of lineage restriction. Biological outcomes that will be assessed in GC treated NSPC cultures at different passages include examination of hormone effects on differentiation.

BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors.

Follow this format for each person. DO NOT EXCEED FOUR PAGES.

NAME MICEVYCH, Paul E

POSITION TITLE

Professor of Neurobiology eRA COMMONS USER NAME (credential, e.g., agency login) MICEVYCH2 EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable.)

INSTITUTION AND LOCATION DEGREE (if applicable) MM/YY FIELD OF STUDY

University of St. Thomas – St. Paul, MN B.A. 1976 Biology University of Minnesota – Minneapolis, MN Ph.D. 1980 Anatomy Mayo Clinic – Rochester, MN Postdoctoral 1982 Neuropharmacology

Please refer to the application instructions in order to complete sections A, B, C, and D of the Biographical Sketch. A. Personal Statement The goal of the proposed research is to continue our dissection of sex steroid action in the nervous system through an examination of the interaction between estradiol signaling in astrocytes and neurons. We have shown that estradiol membrane-initiated signaling requires the transactivaton of metabotropic glutamate receptors (mGluR) to stimulate the synthesis of progesterone in hypothalamic astrocytes. We know turn to examining the neurons interposed between the astrocyte produced neuroprogesterone and the GnRH neurons regulating the LH surge. Over the past 10 years we have developed several assays to examine membrane-initiated signaling and the role of neuroprogesterone. Also, we are expert in dissecting cell signaling pathways that have been associated activation of progesterone synthetic pathways. This proposal offers a truly exciting opportunity to use immortalized adult kisspeptin expressing neuronal cell lines that model the estradiol activated and estradiol inhibited kisspeptin neurons in the hypothalamus. These cell lines will allow us to dissect the interaction of estradiol and neuroprogesterone involved in the regulation of kisspeptin and GnRH release. B. Position and Honors Positions and Employment 1976 -1980 Teaching Assistant, Department of Anatomy, Univ. Minnesota, Minneapolis, MN 1980 -1981 Postdoctoral Fellow (Dr. T. Yaksh, mentor), Dept. Neurologic Surgery, Mayo Clinic, Rochester,

MN 1982 -1983 Instructor, Dept. Anatomy, Mayo Medical School, Rochester, MN 1983 -1992 Assistant Professor, Dept. of Anatomy, Univ. California, Los Angeles (UCLA) 1983 - Member of Brain Research Institute, UCLA 1988-1992 Associate Professor, Dept. of Neurobiology, UCLA 1992- Professor, Dept. of Neurobiology, UCLA 1993- Member, UCLA Intellectual and Developmental Disabilities Research Center (IDDRC) 1993 - 2005 Director, Neurocytology/Cellular Imaging Core Facility, UCLA IDDRC 1994 -1996 Interim Chair, Dept. of Neurobiology, Univ. California, Los Angeles 1997 - 2000 Co-Director, Laboratory of Neuroendocrinology, Brain Research Institute, UCLA 1998- Professor, Division of Head & Neck Surgery, Dept. of Surgery, UCLA 2003- Member, Center for Neurovisceral Sciences & Women’s Health, UCLA 2006 - 2009 Member, Vice Chair, Chair of Council on Academic Personnel, UCLA Division

Other Experience and Professional Memberships 1978 - Member Society for Neuroscience 1978-1989 Member, American Association of Anatomy 1993-2007 Editorial Board, Developmental Neuroscience 1997-1999 &

2010- Member, NSF Scientific Review Panel for the Neuroendocrinology 1998- Member, Society for Behavioral Neuroendocrinology (SBN) 1998-2002 Program Com, SBN 2000-2003 ad hoc Member, IFCN-2/NNB Study Section, NIH 2003-2007 Member NNB Study Section, NIH 2007-2010 Editorial Board, Endocrinology 2007- Editorial Board, Frontiers in Behavioral Neuroscience 2008- ad hoc Member, various Special Emphasis Panels NIH 2009- Editorial Board, J. Neuroscience Research Honors 1976 Delta Epsilon National Honor Society 2008 Wm Evans Fellow, University of Otago, New Zealand C. Selected peer reviewed publications (Selected from 155 peer-reviewed publications)

Most relevant to the current application Micevych, P. E, K. Sinchak, R. H. Mills, L. Tao, P. LaPolt and J.K. H. Lu -- The luteinizing hormone surge is

preceded by an estrogen induced increase of hypothalamic progesterone in ovariectomized and adrenal-ectomized rats. Neuroendocrinology, 78: 29-35, 2003.

Chaban V. V. and P. E Micevych – Estradiol elicits intracellular calcium release in neonatal rat astrocytes. Endocrinology, 145(8): 3788-3795, 2004.

Micevych, P., V.V. Chaban, J. Ogi, J. Lu and K. Sinchak – Progesterone synthesis in hypothalamic astrocytes: intracellular calcium mediated rapid estradiol action. Endocrinology. 48(2):782-789, 2007.

Dewing, P., M. Boulware, K. Sinchak, A. Christensen, P. Mermelstein and P. Micevych -- Membrane associated estrogen receptor-α signals through the mGluR1a to regulate female sexual receptivity. J. Neuroscience. 27(35): 9294-9300, 2007. (PMC2904398)

Dewing, P., A. Christensen, G. Bondar, and P. Micevych -- PKC signaling in the hypothalamic arcuate nucleus regulates sexual receptivity in female rats. Endocrinology, 149(12):5934-42, 2008. PMCID: PMC2613064.

Bondar, G., J. Kuo, N. Hamid and P Micevych -- Trafficking of the membrane estrogen receptor-α. J. Neuroscience, 29 (48): 15323-15330, 2009. (PMC2836237)

Kuo J., G. Bondar, N. Hamid, E. R. Prossnitz and P. Micevych -- Membrane estrogen receptors stimulate intracellular calcium flux and progesterone synthesis in hypothalamic astrocytes. J. Neuroscience, 29:12950-12957, 2010. (PMC2957903)

Kuo, J., N. Hamid, G. Bondar, P. Dewing, J. Clarkson and P. Micevych – Sex differences in hypothalamic astrocyte response to estradiol stimulation. Biology of Sex Differences 1:7, 2010. (PMC3016240)

Dominguez, R. and P. Micevych -- Estradiol rapidly regulates membrane ERα levels in hypothalamic neurons. J. Neuroscience, 30: 12589-12596, 2010. (PMC3049727)

Micevych, P. and M. Kelly - Membrane estrogen receptor regulation of hypothalamic function. Neuroendocrinology. 96(2): 103-110, 2012. (in process)

Christensen, A. and P. Micevych – Caveolin-1 Knockdown in hypothalamus reduces membrane estrogen receptor-α levels and attenuates sexual receptivity. Endocrinol., 153(8):3872-7, 2012.

Dominguez R J. Kuo, P. Dewing and P. Micevych – Trafficking of membrane ERα involved membrane-initiated estrogen signaling in immortalized hypothalamic N-38 neurons. Steroids 78(6): 607-613, 2013.

Micevych, P. and A. Christensen – Membrane-initiated estradiol actions mediate structural plasticity and reproduction. Frontiers in Neuroendocrinol., 33(4):331-41, 2012. (NIHMSID # 401951)

Additional recent publications of importance to the field (in chronological order) Holland K, Popper P, Micevych PE. Antisense oligodeoxynucleotides to CCKA receptor mRNA inhibits lordosis

behavior. Physiol and Behav; 62: 537-543, 1997. Sinchak K, Micevych PE. Progesterone blockade of estrogen activation of µ-opioid receptors regulates

reproductive behavior. J Neuroscience 21: 5723-5729, 2001. Mills RH, Romeo HE, Lu JK, Micevych PE. Site-specific decrease of progesterone receptor mRNA expression

in the hypothalamus of middle-aged persistently estrus rats. Brain Res 955:200-6, 2002. Chaban, V.V., E.A. Mayer, H. S. Ennes and P. E Micevych -- Estradiol inhibits ATP-increased [Ca2+]i in DRG

ganglion neurons. Neuroscience, 118: 941–948, 2003.

Micevych PE, Rissman E, Macias L, Sinchak K. Estrogen receptor is required for estrogen-induced µ-opioid receptor internalization. J Neurosci Res., 71: 802-10, 2003.

Micevych, P. E, K. Sinchak, R. H. Mills, L. Tao, P. LaPolt and J.K. H. Lu -- The luteinizing hormone surge is preceded by an estrogen induced increase of hypothalamic progesterone in ovariectomized and adrenal-ectomized rats. Neuroendocrinology, 78: 29-35, 2003.

Sinchak, K., R. H. Mills, L. Tao, P. LaPolt, J.K. H. and P.E Micevych -- Estrogen induces de novo progesterone synthesis in astrocytes Dev. Neuroscience, 25: 343-348, 2003.

Mills R. H., Sohn, R. K. and P. E Micevych – Estrogen-induced μ-opioid receptor internalization in the medial preoptic area is mediated via neuropeptide Y-Y1 receptor activation in the arcuate nucleus. J. Neuroscience, 24(4): 947-55, 2004.

Saldanha, C, B.A. Schlinger, P.E Micevych and T. Horvath -- Presynaptic NMDA-receptor expression is increased by estradiol in an aromatase-rich area of the songbird hippocampus J. Comp. Neurol 469(4):522-34, 2004.

Sinchak, K, R. H. Mills, C. B Eckersell, and P. E Micevych – Medial preoptic nucleus δ-opioid receptors inhibit lordosis. Behavioral Brain Research, 155(4):301 - 306, 2004.

Soma, K. K., K. Sinchak, A. Lakhter, B.A. Schlinger and P.E. Micevych --Neurosteroids and female reproduction: estrogen increases 3β-HSD mRNA and activity in rat hypothalamus. Endocrinology 146: 4386-4390, 2005.

Chaban V.V. and P.E Micevych – Estrogen attenuation of ATP-induced [Ca2+]i is dependent on membrane associated estrogen receptor-α. J. Neuroscience Res. 81(1):31-7, 2005.

Sinchak, K., K. Shahedi, P. Dewing, and P Micevych -- Sexual receptivity is reduced in the female μ-opioid receptor knockout mouse. NeuroReport. 16:1697-1700, 2005. (PMID16189480)

Sinchak, K., H. E. Romeo, and P. E Micevych -- Estrogen and progestin regulate of OFQ/nociceptin and nociceptin opioid receptor mRNA expression in the female rat limbic hypothalamic system. J. Comp Neurol. 496(2):252-68, 2006. (PMID16538678)

Dewing, P., C. Chiang, K. Sinchak, H. Sim, P. Fernagut, M. Chesselet, P.E Micevych, K. Albrecht, V.R. Harley, and E. Vilain. -- Effect of Sry on dopaminergic neurons and motor behavior. Currents Biology. 16: 415-420, 2006. [Comments in Science and Nature]. (PMID16488877)

Quesada, A., B. Lee and P Micevych -- PI3 kinase/Akt activation mediates estrogen and IGF-1 nigral DA neuronal neuroprotection against a unilateral rat model of Parkinson's disease. Dev Neurobiol. 88(1): 35-42, 2008. (PMC2667142)

Micevych P.E and R. Dominquez – Membrane estradiol signaling in the brain. Frontiers in Neuroendocrinology 30: 315-327, 2009. (PMC2720427)

Chaban, V., J. Li, J.S. McDonald, A. Rapkin, and P. Micevych -- Estradiol attenuates ATP-induced increase of intracellular calcium through group II metabotropic glutamate receptors in rat DRG neurons. J Neuroscience Res., 89: 1707-1710, 2011. (PMC3171520)

Christensen A. and P. Micevych -- CAV1 siRNA reduces membrane estrogen receptor-α levels and attenuates sexual receptivity. Endocrinol. 153(8):3872-7, 2012. (PMC3404361)

Dominguez R J. Kuo, P. Dewing and P. Micevych – Trafficking of membrane ERα involved membrane-initiated estrogen signaling in immortalized hypothalamic N-38 neurons. Steroids. Jun;78(6):607-13, 2013 (PMC3636190)

Christensen A. and P. Micevych.-- A Novel Membrane Estrogen Receptor Activated by STX Induces Female Sexual Receptivity Through an Interaction with mGluR1a. Neuroendocrinology. 2013 Apr 6. [Epub ahead of print] (PMID23571598)

Sinchak, K, P. Dewing, L. Ponce, L. Gomez, A. Christensen, M. Berger, and P. Micevych – GABAB receptors mediate membrane estradiol activation of pro-opiomelanocortin neurons in the arcuate nucleus of the hypothalamus. Hormones & Behavior. In press.

D. Research Support Ongoing Research Support R01 DA 13185 Micevych (PI) 03/01/01 – 02/28/17 NIH/NIDA Sex Steroid Activation of Opioid Circuits in the CNS The major goals of this project are to define the actions of estrogen signaling in NPY neurons that initiate neural events leading to facilitation of lordosis behavior.

BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors.

Follow this format for each person. DO NOT EXCEED FOUR PAGES.

NAME Nancy L Weigel

POSITION TITLE Professor eRA COMMONS USER NAME (credential, e.g., agency login)

NWeigel EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable.)

INSTITUTION AND LOCATION DEGREE (if applicable) MM/YY FIELD OF STUDY

Cornell University, Ithaca, NY BA 1968 Chemistry & Anthropology Johns Hopkins University, Baltimore, MD MA 1972 Biochemistry Johns Hopkins University, Baltimore, MD PhD 1978 Biochemistry Baylor College of Medicine Post-doc 1978-1981 Steroid receptors

A. Personal Statement. My group is interested in nuclear receptor action in prostate and breast cancer and performs basic and translational studies to address the use of these receptors as therapeutic targets. Our work includes studying the role of progesterone receptor and, in collaboration with Dr Fuqua, androgen receptor in breast cancer. In prostate, we are characterizing the functions of androgen receptor splice variants and testing novel approaches to eliminate androgen receptors. In addition, we are testing whether aberrant vitamin D metabolism contributes to aberrant growth in prostate cancer and evaluating a novel metabolism resistant vitamin D receptor agonist.

B. Positions and Honors

Positions and Employment 1968 - 1973 Research Asst for Dr Saul Roseman; Biology, Johns Hopkins University, Baltimore MD 1981 - 1982 Instructor; Cell Biology, Baylor College of Medicine, Houston, TX. 77030. 1982 - 1992 Research Asst Professor; Cell Biology, Baylor College of Medicine, Houston, TX 77030 1992 - 1994 Research Assoc Professor; Cell Biology, Baylor College of Medicine, Houston, TX 77030 1994 - 2001 Associate Professor; Cell Biology, Baylor College of Medicine, Houston, TX 77030 2001- present Professor; Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030

Other Experience and Professional Memberships Editorial Boards: Molecular Endocrinology (1995 – 1998, 2005--2008) Associate Editor 2009--, Steroids (1994 - Present) Endocrinology (2000--2003) Journal of Biological Chemistry (2001--2005) Review Panels: NIH Biochemical Endocrinology; Member 1994 - 1998; NIH Molecular and Cellular Endocrinology 2010-- DOA Breast Cancer Endocrinology study sections 1996,1997,1999; DOA Prostate Cancer Pathobiology study section 1998, 2000;DOA Breast Cancer Pathobiology study section 1998;American Cancer Society Tumor Biochemistry and Endocrinology Study section 1999—2002, chair 2002; DOA Breast Cancer Molecular Biology Study Section Chair 1999-2001, DOA Prostate Cancer Molecular Biology and Genetics study section 2002-2004, DOA Breast Cancer Molecular Biology and Genetics study section 2003-4, Prostate Cancer Endocrinology study section chair 2005; DOA Prostate Cancer Cell Biology I chair 2007, 2008; DOA LCTA study section chair 2010, 2012. Other service: Organizer, Keystone Symposium “Hormonal Regulation of Tumorigenesis” 2005; Organizer, Keystone Symposium “Steroid Sisters”, 2008. Endocrine Society council 2005--2008. DOD PCRP integration panel 2009 Honors and Awards: NIH Postdoctoral Fellow (1979 - 1981), Searle Scholar (1983 - 1986), Marc Dresden Award, 2006; Roy O. Greep award 2008.

B. Selected Peer-reviewed Publications (Selected from >120 peer-reviewed publications)

Most relevant to the current application 1. Agoulnik IU, Krause WC, Bingman WE 3rd, Rahman HT, Amrikachi M, Ayala, GE, Weigel NL (2003)

Repressors of androgen and progesterone receptor action. J Biol Chem 278(33):31136-48. PMID: 12771131

2. Agoulnik IU, Vaid A, Bingman WE 3rd, Erdeme H, Frolov A, Smith CL, Ayala G, Ittmann MM and Weigel NL (2005) A Role for SRC-1 in Promoting Prostate Cancer Cell Growth and Tumor Progression Cancer Research 65(17):7959-67. PMID: 16140968

3. Agoulnik IU, Vaid A, Nakka M, Alvarado M, Bingman WE 3rd, Erdem H, Frolov A, Smith CL, Ayala GE, Ittmann MM and Weigel NL. Androgens Modulate Expression of TIF2, an Androgen Receptor Coactivator whose Expression Level Correlates with Early Biochemical Recurrence in Prostate Cancer. Cancer Research 66(24):10594-602. PMID: 17079484

4. Agoulnik IU, Bingman WE, Nakka M, Li W, Wang Q, Liu XS, Brown M, Weigel NL (2008) Target gene-specific regulation of androgen receptor activity by p42/p44 mitogen-activated protein kinase. Mol. Endocrinol. 22:2420-2432. PMID: 18787043

5. He S, Zhang C, Shafi AA, Sequeira M, Acquaviva J, Friedland JC, Sang J, Smith DL, Weigel NL, Wada Y, Proia DA. Potent activity of the Hsp90 inhibitor ganetespib in prostate cancer cells irrespective of androgen receptor status or variant receptor expression. Int J Oncol. 2013 Jan;42(1):35-43. doi:10.3892/ijo.2012.1698. Epub 2012 Nov 14. PubMed PMID: 23152004.

6. Nakka M, Agoulnik IU, Weigel NL. Targeted disruption of the p160 coactivator interface of androgen receptor (AR) selectively inhibits AR activity in both androgen-dependent and castration-resistant AR-expressing prostate cancer cells. Int J Biochem Cell Biol. 2012 Dec 25. doi:pii: S1357-2725(12)00408-6.10.1016/j.biocel.2012.12.012. [Epub ahead of print] PubMed PMID: 23270728.

7. Shafi AA, Cox MB, and Weigel NL (2013) Androgen Receptor Splice Variants are Resistant to Inhibitors of Hsp90 and FKBP52, which alter Androgen Receptor Activity and Expression. Steroids in press

Additional recent publications of importance to the field (in chronological order) 8. Narayanan R, Adigun AA, Edwards DP and Weigel NL (2005) Cyclin dependent kinase activity is required

for progesterone receptor function: a novel role for cyclin A/cdk2 as a progesterone receptor coactivator. Mol Cell Biol 25(1):264-77. PMID: 15601848

9. Narayanan R, Edwards DP and Weigel NL (2005) Human Progesterone Receptor Displays Cell Cycle Dependent Changes in Transcriptional Activity. Mol Cell Biol 25(8):2885-98. PMID: 15798179

10. Stewart LV, Lyles B, Lin M-F and Weigel NL (2005) Vitamin D Receptor Agonists Induce Prostatic Acid Phosphatase to Reduce Cell Growth and HER-2 Signaling in LNCaP-Derived Human Prostate Cancer Cells. J Steroid Biochem Mol Biol 97(1-2):37-46. PMID: 16076555

11. Proia DA, Nannenga BW, Donehower LA, Weigel NL (2006) Dual Roles for the Phosphatase PPM1D in Regulating Progesterone Receptor (PR) Function. J Biol Chem 281(11):7089-101. PMID: 16352595Phillips Rohan JN and Weigel NL (2009) 1,25(OH)2D3 reduces c-Myc expression, inhibiting proliferation. Endocrinology 150(5):2046-54.

12. Washington MN, Weigel NL. (2010) 1α,25-Dihydroxyvitamin D3 Inhibits Growth of VCaP Prostate Cancer Cells Despite Inducing the Growth-Promoting TMPRSS2:ERG Gene Fusion. Endocrinology 151:1409-17. Epub 2010 Feb 10. [Epub ahead of print] PubMed PMID: 20147525.

13. Washington MN, Kim JS, Weigel NL. (2011) 1α,25-dihydroxyvitamin D3 Inhibits C4-2 Prostate Cancer Cell Growth via a Retinoblastoma Protein (Rb)-Independent G1 Arrest. Prostate. 71:98-110. PubMed PMID: 20632309

14. Hodgson MC, Shao LJ, Frolov A, Li R, Peterson LE, Ayala G, Ittmann MM, Weigel NL, Agoulnik IU (2011). Decreased expression and androgen regulation of the tumor suppressor gene INPP4B in prostate cancer. Cancer Res. 71:572-82. Epub 2011 Jan 11. PubMed PMID: 21224358; PubMed Central PMCID:

15. Moore NL, Weigel NL. (2011) Regulation of progesterone receptor activity by cyclin dependent kinases 1 and 2 occurs in part by phosphorylation of the SRC-1 carboxyl-terminus. Int J Biochem Cell Biol. ;43:1157-

67. doi:10.1016/j.biocel.2011.04.009. Epub 2011 Apr 21. PubMed PMID: 21550420; PubMed Central PMCID: PMC3124765.

C. Research Support

Ongoing Research Support DOD training grant W81XWH-12-1-0010 (Weigel) 04/15/12-04/14/15 DOD Prairie View A&M/Baylor College of Medicine SMART Summer Undergraduate Prostate Cancer Research Project (summer research training for underrepresented minorities) PCF award (O’Malley) 9/1/2012-8/31/2014 Targeting the p160 steroid receptor coactivators (SRCs) as a novel approach for the treatment of castration-resistant prostate cancer (CRPC) The Weigel portion of this proposal is to perform a high throughput assay to identify small molecules that interrupt the amino-terminal interface between the androgen receptor and SRC-1 and to test the responsiveness of CRPC models to inhibition of this interaction. DOD Idea award W81XWH-13-1-0330 (Weigel) 9/7/2013—9/06/2016 Counteracting Aberrant Vitamin D Metabolism in Prostate Cancer Grant Specialist Kenneth Grenier KENNETH.E.GRENIER.CIV@MAIL.MIL, 820 ChandlerStreet, Fort Detrick MD 21702 The goals of this proposal are to determine whether aberrant vitamin D metabolism causes prostate cell growth and to test a novel VDR agonist as a means to prevent growth. Completed Research Support DOD Idea Award W81XWH-09-1-0416 (Weigel) 06/1/09 – 05/31/12 DOD Prostate Cancer Research Program TMPRSS2-ERG gene fusions and Vitamin D Action in Prostate Cancer This project seeks to understand the regulation of the TMPRSS2/ERG fusion gene by vitamin D, the functional interactions of VDR and AR signaling in regulating the gene, and effects of ERG expression on CYP24 expression. R01 CA57539-15A2 (Weigel) 08/01/06 – 07/31/12 (one year no cost) NIH Regulation of Human Steroid Receptors by Phosphorylation Grant Specialist: Kent Hevner, kent@mail.nih.gov, NIH/NCI, FVC - Fairview Ctr (FCRDC), 300

Fort Detrick, Frederick, MD The goals of this grant are to determine the roles of selected progesterone receptor phosphorylation sites in regulating gene expression, to determine the effects of one of the sites on biological responses by generating and characterizing a mouse model that expresses mutant receptor and to use a mammary gland reconstitution system to determine the role of additional sites in mammary gland development. OVERLAP: none