Overview
Our lab focuses on the prototypical second messenger cyclic AMP (cAMP). Adenylyl cyclases produce cAMP, and in mammalian cells there are two distinct classes of adenylyl cyclase, a family of heterotrimeric G-protein responsive, transmembrane adenylyl cyclases (tmACs; ADCY1-9) and the bicarbonate-regulated soluble adenylyl cyclase (sAC; ADCY10). Our combined laboratory purified and cloned sAC. Despite its more recent discovery, sAC represents the primordial cyclase in mammals. In contrast to tmACs, which are modulated by heterotrimeric G proteins in response to extracellular signals acting through seven-transmembrane spanning, G protein-coupled receptors, sAC is directly regulated by intracellular signals such as bicarbonate and calcium ions. In biological systems, carbonic anhydrases equilibrate bicarbonate ions with carbon dioxide and pH nearly instantaneously. Via this equilibrium, sAC and sAC-like cyclases throughout all kingdoms of life serve as “Natures carbon dioxide/bicarbonate/pH sensors.”
Our laboratory studies sAC-dependent physiologic processes using genetically modified knockout and knock-in mouse models, cell-lines, antibodies, and multiple selective pharmacologic inhibitors developed in the lab. Current projects can be separated into to two broad categories: discovery of sAC physiologic functions and drug discovery efforts.
In mammals, sAC is most abundantly expressed in male germ cells, and it is proven to be essential for male fertility in mice and men. sAC is responsible for generating the cAMP which is required for sperm motility and the maturation processes that occur after ejaculation during transit through the female reproduction tract. In addition to studying these sAC-dependent, cAMP mediated processes, we are attempting to develop sAC specific inhibitors into novel, non-hormonal contraceptives for men and women.
For further information see the Levin/Buck Lab Website: Dr. Levin's Lab
Highlights
- 1Nature communications · 2023
- 2Molecular human reproduction · 2021
- 3Proceedings of the National Academy of Sciences of the United States of America · 2025
Publications
Funding
Active
5 grants- MPIP50HD123367-01Advancing an ADCY10 inhibitor on-demand male contraceptive into humansEunice Kennedy Shriver National Institute of Child Health and Human Development · 2026–2030
- MPIR01AI175437-01A1A Novel, Multi-compartment Intravaginal Ring for Prevention of Genital Herpes and Unintended Pregnancy.National Institute of Allergy and Infectious Diseases · 2024–2029 · via Oak Crest Institute of Science
- MPIR01HD111549-01A1Optimization of lead candidates for an on-demand male contraceptiveEunice Kennedy Shriver National Institute of Child Health and Human Development · 2023–2028
- MPIR01HD088571-06A1Comparative studies on the regulation of metabolism during sperm capacitationEunice Kennedy Shriver National Institute of Child Health and Human Development · 2017–2027· 3 renewals
- MPIP50HD113015-03On-demand nonhormonal male contraception via ADCY10 inhibitionEunice Kennedy Shriver National Institute of Child Health and Human Development · 2023–2026
Completed grants (17)
- Co-I7200AA22CA00002Microbicide R&D to Advance HIV Prevention Technologies through Responsive Innovation and eXcellence, MATRIXUnited States Agency for International Development · 2021–2025 · via Oak Crest Institute of Science
- KPMCI 224694-01Assessing safety of soluble adenylyl cyclase inhibitors validated as lead compounds for on demand male contraceptives.Male Contraceptive Initiative · 2022–2024
- PIMCI 231731-02ADCY10 inhibitors as pre-coital, 'on-demand', non-hormonal male contraceptivesMale Contraceptive Initiative · 2022–2024
- KPF31HD105363-01Discovery and Characterization of an Endogenous Inhibitor of Soluble Adenylyl CyclaseEunice Kennedy Shriver National Institute of Child Health and Human Development · 2021–2024Fellowship
- KPMCI 214459-01In vivo consequences of on-demand contraception by sAC inhibitorsMale Contraceptive Initiative · 2021–2023
- MPIR01AG061290-04High Throughput screen to identify "first of their kind" activators of ADCY10National Institute on Aging · 2019–2023
- PIMCI-223430-01ADCY10 inhibitors as pre-coital, 'on-demand', non-hormonal male contraceptivesMale Contraceptive Initiative · 2022–2023
- MPIP50HD100549-03On-Demand Pharmacological Contraception by Blocking ADCY 10Eunice Kennedy Shriver National Institute of Child Health and Human Development · 2019–2022
- KPMCI 194496-01Male Contraceptive Trainee Fellowship - 2019Male Contraceptive Initiative · 2019–2021
- Co-I180012-01"First of their Kind" Activators of Soluble Adenylyl Cyclase for the Treatment of GlaucomaDaedalus Fund for Innovation (Weill Cornell) · 2017–2020
- PIR01GM107442-04Metabolic Regulation via Intramitochondrial sACNational Institute of General Medical Sciences · 2014–2018
- KPR21EY025810-02Modulating Intraocular Pressure to Treat Ocular Hypotony and GlaucomaNational Eye Institute · 2015–2017
- PIR01HD059913-05Soluble Adenylyl Cyclase Isoforms Essential for Male FertilityEunice Kennedy Shriver National Institute of Child Health and Human Development · 2009–2014
- KPR01GM062328-12Bicarbonate Regulated Adenylyl CyclaseNational Institute of General Medical Sciences · 2010–2014
- PIR01HD038722-04SOLUBLE ADENYLYL CYCLASE ACTIVITY IN MALE GERM CELLSNICHD · 2001–2005 · via NIH RePORTER
Available technologies
Show 2 more technologies
- 9143
News mentions
- Weill Cornell Medicine Receives NIH Grant to Test Novel Male ContraceptiveOctober 23, 2026
Weill Cornell Medicine has received a four-year, $8.2 million grant from the National Institute of Child Health and Human Development (NICHD) to develop and test an experimental on-demand male contraceptive pill that temporarily stops sperm in their tracks.
- NIH Center Grant Bolsters Male Contraceptive ResearchSeptember 21, 2023
Weill Cornell Medicine has received a three-year, nearly $6 million grant to lead one of three national contraceptive research centers.
- On-Demand Male Contraceptive Shows Promise in Preclinical StudyFebruary 14, 2023
An experimental contraceptive drug candidate developed by Weill Cornell Medicine investigators temporarily stops sperm in their tracks and prevents pregnancies in preclinical models.
- Sixth Annual Symposium on Entrepreneurship and Academic Drug Development Highlights Expanding Entrepreneurial EcosystemNovember 17, 2022
The sixth annual Symposium on Entrepreneurship and Academic Drug Development, hosted Nov. 14, showcased Weill Cornell’s rich array of programs for supporting faculty who want to bring their discoveries to the health care marketplace.
Media highlights
- Experimental Male Contraceptive Pill May Immobilise Sperm, Work Within 30 Minutes & Give Protection For 8 HoursHealth And Me · October 27, 2026
- Scientists Developing Male Birth Control Pill To Take 30 Minutes Before SexNewsweek · October 26, 2026
- AT A GLANCE: Male Birth ControlCrain's New York Health Pulse · October 23, 2026
Mentoring
- JFJacob FerreiraPharmacology (PhD) · Class of 2024
- TRThomas RossettiPharmacology (PhD) · Class of 2023
- SWShakarr WigginsNeuroscience (PhD) · Class of 2023
- NRNatalia Rivera-SanchezPharmacology (PhD)
External relationships
Leadership Roles
Sacyl Pharmaceuticals, Inc.
Ownership
FemFort Contraception LLC · Sacyl Pharmaceuticals, Inc.
Advisory/Scientific Board Member
Sacyl Pharmaceuticals, Inc.
Proprietary Interest
EMD Millipore Corporation · Sacyl Pharmaceuticals, Inc.