About

Professor Seth M. Cohen is the Principal Investigator of the Cohen laboratory at the University of California, San Diego. He is a graduate of Stanford University and the University of California, Berkeley. Following his graduate studies, he conducted postdoctoral research at the Massachusetts Institute of Technology (M.I.T.). Professor Cohen founded the Cohen laboratory in July 2001. The Cohen research group at UCSD is composed of a diverse team including undergraduate and graduate students, postdoctoral researchers, and visiting scholars with expertise spanning chemistry, biochemistry, and materials science. The group values diversity, collaboration, and fosters an inclusive environment that supports both individual and collective success.

Research topics

• Chemistry
• Nanotechnology
• Organic chemistry
• Computer Science
• Materials science
• Family medicine
• Physics
• Combinatorial chemistry
• Computational biology
• Biochemistry
• Nursing
• Stereochemistry
• Internal medicine
• Medicine
• Polymer science
• Composite material

Selected publications

• Introducing “In Focus: Basic Research to Broader Impacts”

  ACS Central Science · 2026-04-22

  articleOpen accessSenior author
  PublisherDOI

• Inter-ligand cross-links determine secondary building unit formation in oligoMOFs

  Dalton Transactions · 2026-01-01

  articleSenior author

  SBU bridged by carboxylate ligands. These results are the first examples of tether length influencing SBU chemistry in MOFs and help understand the interplay between the MOF lattice and the geometric constraints imposed by inter-ligand cross-links in oligoMOFs.

  PublisherDOI

• Abstract PS1-02-16: Addressing the support needs of people with hereditary cancer risk through virtual peer-led meetings

  Clinical Cancer Research · 2026-02-17

  article

  Abstract Background: People with pathogenic variants (PV) associated with hereditary cancer risk face psychosocial challenges, including anxiety about risk-management, family communication, and feelings of isolation. While clinical guidelines are well-established for many genes linked to cancer risk, emotional support remains an unmet need. FORCE is a national nonprofit organization serving people affected by hereditary cancer risk. We provide virtual support meetings tailored for the hereditary cancer community. The meetings are organized by topic (e.g. mastectomy), situation (e.g. survivor, previvor, caregiver), gene (e.g. BRCA1/2, Lynch syndrome, others), and other factors. The meetings are co-led by genetics experts and trained FORCE peer volunteers. Past studies show that women with hereditary cancer risk experience significant emotional distress, and value referrals from their doctors to social support networks3. Perceptions of low social and emotional support are predictors of increased distress and poor mental health outcomes in this population. However, structured support groups, peer connections, and family-based emotional support improve coping, anxiety levels, and patient experience1-3.Integrating emotional support into hereditary cancer care meets a critical need and can improve patient outcomes. Methods: Between February and July 2025, 1000 people attended 40 FORCE virtual support meetings for people affected by hereditary cancer risk. Feedback was collected from 185 attendees via a post-meeting survey to assess satisfaction, emotional support, and perceived value of information gained. Participants could also provide open-ended feedback. Results: Participants expressed that the meetings provided a safe, inclusive space to connect with others facing similar challenges, helped reduce feelings of isolation, and validated participant’s emotions: •62.4% felt less anxious or worried. •87.5% felt more supported or less alone. •82.3% felt more confident in their knowledge.•65.9% felt more confident about their decisions.•94% were “very satisfied" (71.2%) or “satisfied” (22.8%). •Attendees received support on various topics including genetic counseling/testing (40%), breast reconstruction (34%) and communication with healthcare providers (33%).Qualitative Themes: •Greater sense of community: “The support group is the only outlet for me to express my hopes, frustrations and fears.”•Empowerment in medical decision-making: “I am definitely going through with my mastectomy and am so happy I met new friends to help me through my journey!”• Improved representation: Specific groups (e.g., LGBTQ+, young previvors) felt especially seen when breakout sessions included people who shared their lived experiences. Discussion: The emotional burden of navigating hereditary cancer risk can be substantial. Survey responses demonstrated that FORCE’s peer-and-expert-led virtual meetings create a needed space for people with hereditary cancer risk to process complex emotions, build resilience, and make informed decisions. Organizing meetings by topic highlights the diversity of attendees and the importance of tailored support meetings. Conclusion:Virtual support meetings represent a scalable, low-cost, and high-impact intervention to address the emotional needs of people with hereditary cancer risk. The positive reception underscores the value of integrating psychosocial support alongside clinical care. References: 1.https://doi.org/10.1080/10410236.2016.1250187 2.FORCE. (2024, October 21). Results from FORCE’s 2024 Survey Highlighting the Needs of People at High Risk for Breast Cancer. FORCE Blogs. 3.https://doi.org/10.3389/fpsyt.2019.00208 Citation Format: J. D. Rogers, S. Cohen, M. Rosas, P. Welcsh, K. N. Owens, S. J. Friedman, R. H. Pugh Yi. Addressing the support needs of people with hereditary cancer risk through virtual peer-led meetings [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-02-16.

  PublisherDOI

• Hydrophobic Metal–Organic Frameworks Enable Superior High-Pressure Ammonia Storage through Geometric Design

  Journal of the American Chemical Society · 2026-01-17

  article

  Hydrophobic metal–organic frameworks (MOFs) are typically overlooked for ammonia storage due to weak host–guest interactions. Here, we demonstrate that four structurally analogous aluminum-based MOFs exhibit a counterintuitive behavior whereby framework geometry, rather than ligand hydrophilicity, determines high-pressure NH3 adsorption performance. The hydrophobic CAU-23 achieved an exceptional capacity matching hydrophilic analogs despite its poor low-pressure uptake. This pressure-dependent enhancement stems from the unique 4-cis-4-trans geometry of CAU-23 compared to the purely cis arrangement of MIL-160 and KMF-1 and the alternating cis-trans configuration of MOF-303. Critically, CAU-23 retained 95% capacity over three high-pressure cycles, whereas hydrophilic MOFs suffered 39–46% irreversible losses due to strong NH3-framework interactions that compromise structural integrity. Grand canonical Monte Carlo simulations reveal that high pressure enables NH3 clustering through intermolecular hydrogen bonding, bypassing the need for strong host–guest interactions. High-pressure powder X-ray diffraction measurements confirm the exceptional mechanical resilience of CAU-23, showing complete structural recovery upon decompression despite exhibiting the highest pressure sensitivity among the studied MOFs. An extended analog, HE-CAU-23, validates this design principle with further enhanced capacity. These findings reveal a paradigm shift toward hydrophobic MOFs with optimized geometry for high-performance and regenerable gas storage applications.

  PublisherDOI

• Probing the External Surface Chemistry of Imine-Based Covalent Organic Frameworks Using Reactive Organic Dyes

  Journal of the American Chemical Society · 2026-03-19

  articleSenior authorCorresponding

  The external surfaces of covalent organic frameworks (COFs) are presumably composed of free terminal functional groups from their constituent monomers. These terminal groups have been utilized to immobilize molecules onto COF surfaces for a variety of studies and potential applications. Despite the utility of these latent functional groups for COF functionalization and composite formation, the surface chemistry of the COFs has not been quantitatively investigated and is not well understood. In this work, fluorescent organic dyes bearing reactive amine and aldehyde functional groups are used to probe the surface chemistry of representative two-dimensional (2D) imine-based COFs. Systematic dye binding and displacement experiments provide new insights into the characteristics of COF surfaces and the reactivity of different molecules with the surface groups on the COF crystallites.

  PublisherDOI

• Metal‐Binding Pharmacophores in Metalloenzyme Drug Discovery

  2026-04-22

  otherSenior author
  PublisherDOI

• A phase II trial of pembrolizumab plus olaparib for the treatment of patients with persistent/recurrent endometrial cancers.

  Journal of Clinical Oncology · 2025-05-28

  article

  5597 Background: Copy number-high (CNH) ECs are characterized by high levels of copy-number alterations and TP53 mutations, and a subset may have a homologous recombination-deficiency (HRD) phenotype. The presence of an HRD-phenotype within CNH EC provides the rationale for using OLA in combination with PEM, as this exploits the mechanism of immune priming which creates further genomic instability and drives immune response. Methods: This is an investigator-initiated, single- arm, open-label, phase II trial evaluating the efficacy and safety of PEM + OLA in pts with persistent/recurrent TP53 -mutant EC. Key eligibility criteria included age ≥18 years, measurable disease, £3 prior lines of therapy, all histologic types allowed with aberrant p53 IHC and/or mutant TP53 . Carcinosarcomas were eligible if the epithelial component met the p53/ TP53 criteria. dMMR/MSI-H and POLE hotspot tumors were not eligible. All were PEM and OLA naïve and received OLA orally at 300mg every 12 hours and PEM 200mg every 3 weeks IV. Primary endpoint was objective response rate (ORR) by 24 weeks per RECIST 1.1. Results: At data cut off (December 12, 2024), 26 patients (pts) initiated therapy and 25 pts were evaluable for efficacy. Median age was 68 years (range:59-83). 13 pts (50%) had serous, 8 pts (31%) were mixed/high grade, and 4 pts (15%) had carcinosarcoma histology. 24 pts (92%) had 1 line of prior chemotherapy. 1 pt had a germline BRCA2 and 1 pt had a somatic BRCA1 mutation. 2 pts achieved complete response (CR), 6 pts achieved partial response (PR), resulting in an ORR of 32% (90% one-sided CI: 19.6-100%). Median duration of response was 10.5 months (80% CI:6.4-11.8). Median progression-free survival (PFS) was 4.8 months (80% CI: 3.6-5.9), and median overall survival (OS) was 21.2 months (80% CI: 9.4-NE). 50% (2/4) of carcinosarcoma pts achieved CR and PR, respectively. Most common ≥ grade 3 treatment related adverse events were anemia (12%), neutropenia (19%). 1 pt developed grade 3 pneumonitis, 2 pts developed grade 2 adrenal insufficiency. No new safety signals were identified. Conclusions: The combination of PEM + OLA has promising activity with durable responses observed in pts with persistent/recurrent TP53 -mutant EC, including carcinosarcomas. Molecular subtype selection is critical in further investigation of this combination. Clinical trial information: NCT05156268 .

  PublisherDOI

• Substituent size versus metal binding of inhibitors with variants of influenza endonuclease

  Journal of Inorganic Biochemistry · 2025-12-31 · 1 citations

  articleOpen accessSenior authorCorresponding

  The influenza virus causes a significant burden of illness each year, affecting billions of people worldwide. Although vaccination is the most effective method to prevent seasonal influenza infection, viral escape mechanisms make vaccine composition difficult to predict. Antivirals are crucial for decreasing rates of morbidity and mortality from influenza viral infection. The newest anti-influenza drugs target the RNA-dependent RNA polymerase acidic N-terminal (PA N ) endonuclease, a critical component of influenza viral replication machinery. This study examines the structure of inhibitors of PA N that utilize a hydroxypyridinone-based metal-binding pharmacophore (MBP). Specifically, this report explores how the size of substituent groups impacts the binding conformation and affinity of a series of compounds against both wild-type (WT) and resistance mutant strains, I38T and E23K. Co-crystal structures revealed that the distance between compounds and residue 38 was conserved to maintain ideal interactions, resulting in deviations from ideal coordination geometries at the active site metal centers. This suggests the interactions with residue 38 with each compound is very important and can impact inhibitor potency as a consequence of distortions in the metal binding geometry of the compounds. Binding of inhibitors to the dinuclear active site of influenza endonuclease is modulated by distal interactions to protein residues outside the metal ion coordination sphere. These distal interactions can have a substantial impact on inhibitory activity.

  PublisherDOI

• Controlling the Mechanical Response of Polymers via Metal Induced Coordination Conformational Changes

  Angewandte Chemie International Edition · 2025-07-24

  articleOpen accessSenior authorCorresponding

  Abstract The modulation of mechanical properties in polymers with metal binding ligands has largely been achieved via crosslinking between polymer chains induced by metal ion binding to pendant or end ligating groups. In this work, incorporation of ethylenediaminetetraacetic acid (H 4 edta) into the main chain backbone of flexible, linear polymers results in substantial modulation of mechanical properties via conformational changes in the imbedded ligand within the polymer backbone induced by metal ion binding. Upon the addition of metal ions, these polymers transform from viscous liquids into solids with improved elastic characteristics. Polymer strength and toughness are significantly enhanced without the need for extensive polymer crosslinking. This approach represents a new paradigm in using metal ions to modulate the mechanical properties of organic polymers.

  PublisherOA PDFDOI

• Controlling the Mechanical Response of Polymers via Metal Induced Coordination Conformational Changes

  Angewandte Chemie · 2025-07-24

  articleSenior authorCorresponding

  Abstract The modulation of mechanical properties in polymers with metal binding ligands has largely been achieved via crosslinking between polymer chains induced by metal ion binding to pendant or end ligating groups. In this work, incorporation of ethylenediaminetetraacetic acid (H 4 edta) into the main chain backbone of flexible, linear polymers results in substantial modulation of mechanical properties via conformational changes in the imbedded ligand within the polymer backbone induced by metal ion binding. Upon the addition of metal ions, these polymers transform from viscous liquids into solids with improved elastic characteristics. Polymer strength and toughness are significantly enhanced without the need for extensive polymer crosslinking. This approach represents a new paradigm in using metal ions to modulate the mechanical properties of organic polymers.

  PublisherDOI

Recent grants

• NIH Grant R03AI070651

  NIH · $153k · 2010

• Insight and Optimization of Metalloprotein Inhibitors

  NIH · $2.2M · 2011–2020

• Metal-binding Isosteres for Influenza Endonuclease Inhibitors and Beyond

  NIH · $1.8M · 2020–2026

• Engineering Metal-Organic Framework Catalysts using Advance Functionalization Techniques

  NSF · $450k · 2014–2017

• Developing Metallo-Beta-Lactamase Inhibitors

  NIH · $2.3M · 2015–2021

Frequent coauthors

• Mark Kalaj

  97 shared

• D.T. Puerta

  73 shared

• Johannes Karges

  Ruhr University Bochum

  68 shared

• Benjamin L. Dick

  University of California, San Diego

  58 shared

• Hyeonglim Seo

  53 shared

• J. Andrew McCammon

  University of California, San Diego

  50 shared

• S.R. Halper

  The Aerospace Corporation

  50 shared

• Kenneth N. Raymond

  49 shared

Labs

• Cohen Research GroupPI

  Our team consists of a diverse group of undergraduate students, graduate students, postdoctoral researchers, and often visiting scholars that have a rich expertise in chemistry, biochemistry, and materials science.

Education

• B.S., Chemistry and Political Science

  Stanford University

• Ph.D.

  University of California, Berkeley

• Other

  Massachusetts Institute of Technology

Awards & honors

• NSF CAREER award
• ACS Cope Scholar Award
• 2004 Cottrell Scholar
• 2017 TREE
• 2022 IMPACT awards from RCSA