Kate Coleman, Ph.D., CAPM

Yarrow Biotechnology was an RTW-incubated startup company focused on developing monoclonal antibody therapeutics for autoimmune and cardiometabolic disorders. In my role as Senior Scientist, I led development of functional cell-based assays to assess antibody leads and initiated cell line development and reagent validation to start a new program.

Concarlo Therapeutics is developing small molecule inhibitors targeting the cell cycle regulator p27 as a strategy to inhibit proliferation of drug-resistant cancers. As Principal Scientist, I established cell-based assays to assess in vitro efficacy of small molecule candidates, including BrdU ELISA assays and flow cytometry analysis of cell cycle distribution. I also provided technical guidance for outsourced projects with CRO partners.

Department of Biochemistry & Molecular Pharmacology Mentor: Dr. Tony T. Huang A major focus of the Huang lab is on the regulation of deubiquitylating enzymes (DUBs) and understanding their roles in modulating DNA replication and repair. My work investigated a unique regulatory mechanism for one such DUB, USP1, following up on the discovery that USP1 self-inactivates by cleaving itself internally following UV irradiation. I showed using a variety of cell-based experiments, including single-molecule DNA fiber assays, Western blotting, and super-resolution microscopy, that defects in USP1's autocleavage mechanism cause USP1 molecules to become trapped on DNA, contributing to replication stress and genome instability in cancer cells (Coleman et al., 2022). For this project as well as several others, I established and led collaborations with cross-functional teams at NYU in genomics, proteomics, and super-resolution microscopy. I regularly utilized mammalian cell culture, CRISPR-based genome engineering, fluorescence microscopy, and Western blotting approaches in mechanistic studies. Links to publications: SLFN11 counteracts the RFWD3-PRIMPOL DNA damage tolerance axis to restrain gapped DNA synthesis in response to replication stress https://www.nature.com/articles/s41467-025-66068-1 USP1-trapping lesions as a source of DNA replication stress and genomic instability: (https://www.nature.com/articles/s41467-022-29369-3) SENP8 limits aberrant neddylation of NEDD8 pathway components to promote cullin-RING ubiquitin ligase function https://elifesciences.org/articles/24325

Curriculum in Genetics & Molecular Biology Mentor: Dr. Jeanette G. Cook Jean Cook's lab studies the regulation of the mammalian cell cycle with emphasis on proteins involved in DNA replication, genome stability, and quiescence/senescence. My dissertation research focused on control of protein destruction at the G1/S transition by the E3 ubiquitin ligase CRL4Cdt2. I discovered that substrates of this single E3 ligase are not degraded simultaneously upon S phase entry, but rather in a defined order. Changing the degradation order of substrates contributed to replication stress and genome instability (Coleman et al., 2015). This project involved molecular cloning to create substrates with swapped E3 targeting sequences (PIP degrons), cell line engineering, Western blotting, and a collaboration with the lab of Jeremy Purvis to monitor substrate degradation kinetics by live-cell imaging analysis. Additional experience: Teaching Assistant, Principles of Biology, 2011 TIBBS program teaching certification, 2011 HHMI Future Scientists & Clinicians Program Mentor, Summer 2012 & 2013 Student-invited speaker selection committee, 2014 Link to publication: Sequential replication-coupled destruction at G1/S ensures genome stability: (http://genesdev.cshlp.org/content/29/16/1734.long)

DFCI Cancer Vaccine Center Supervisors: Dr. Ellis Reinherz and Dr. Likai Song Responsible for reagent preparation and structural analysis of the HIV gp41 protein using EPR and SPR methods. Links to publications: Broadly neutralizing anti-HIV-1 antibodies disrupt a hinge-related function of gp41 at the membrane interface: http://www.pnas.org/content/106/22/9057.long