rxp618

Richard Pomerantz, PhD

Contact Dr. Pomerantz

233 South 10th St
Bluemle Life Sciences Building Room 915
Philadelphia, PA 19107


Medical School

PhD in Molecular and Cellular Biology, State University of New York, Downstate Medical Center, Brooklyn, NY - 2006

Laboratory research

My laboratory is primarily interested in understanding how human DNA repair factors function and contribute to genome integrity and instability in normal and cancer cells, respectively. Current areas of interest include investigating mutagenic double-strand break repair pathways, such as alternative end-joining which contributes to genome instability and promotes the proliferation of cancer cells that are mutated in tumor suppressor genes BRCA1/2. Because backup double-strand break repair pathways are essential for the proliferation of BRCA deficient cancer cells, we are interested in developing factors that promote these pathways as anti-cancer drug targets. For example, we aim to develop inhibitors of DNA polymerase theta for targeting BRCA deficient cancers for killing, which is important for the development of personalized medicine in breast, ovarian and other cancers defective in homology-directed repair, including leukemias. Lastly, my laboratory is also interested in developing novel DNA and RNA synthetic biotechnologies and investigating the interplay between RNA and DNA metabolism, such as potential roles for RNA in DNA repair.

Contributions to Science

Mechanisms of Alternative End-Joining. My laboratory has elucidated the mechanism of microhomology-mediated end-joining (MMEJ) promoted by DNA polymerase q (Polq), and was the first to show that this polymerase facilitates MMEJ in human cells. MMEJ—also referred to as alternative end-joining (alt-EJ)—is an error-prone DNA repair process that promotes chromosome translocations in human cells and chemotherapy resistance. We also elucidated the mechanism by which Polq performs terminal transferase activity at DNA repair junctions and have patented this process for potential applications in biotechnology. In a more recent studies, we discovered that the helicase domain of Polq promotes MMEJ by counteracting RPA and performing DNA annealing, and have elucidated how the 290 kDa full-length Polq polymerase-helicase protein facilitates MMEJ. These studies provide key insights into the biochemical mechanisms responsible for chromosomal translocations and genome instability observed in cancer cells.

Interplay of RNA and DNA Metabolism. In a new area of research, may lab has elucudated novel mechanisms of RNA-transcript mediated DNA repair involving human RAD52. These studies are the first to reconstitue RNA-dependent DNA recombinational repair in vitro and suggest that RNA-mediated DNA repair can be facilitated by reverse transcriptase-independent and dependent mechanisms.

As a postdoctoral associate at Rockefeller University, I identified novel mechanisms of replication bypass of transcription complexes. Since the causes and consequences of replication-transcription conflicts are still not well understood, this area of study remains highly relevant in both bacteria and eukaryotic cells.

Mechanisms of Precision Medicine. My lab is actively seeking ways to selectively kill cancer cells deficient

in the BRCA1/2 tumor suppressor proteins with novel small-molecule inhibitors. Towards this goal, we have

identified inhibitors of RAD52 and Polymerase θ which promote the proliferation of BRCA deficient cells. This

work is focused on developing new drugs for precision medicine.

Mechanisms of RNA Transcription. During my graduate research, I discovered a novel mechanism of nucleotide incorporation involving template slippage that is universal among RNA polymerases and appears to be common for most nucleic acid enzymes including DNA polymerases and ribosomes. During this time, I also developed T7 RNA polymerase as an information dependent molecular motor for potential applications in nanotechnology. This technology is currently being adapted for genome sequencing applications.

Honors and Awards

2003                    American Society for Microbiology Research                                 Travel Award                                                                                                 Bio-, Micro-, and Nanosytems Conference,                                 New  York, NY

2003                    NASA Research Travel Award                                  Trends in Nanotechnology Conference,                                 Salamanca, Spain

2005                    Biophysical Society Research Travel                                 Award                                                                                                            49th Annual Meeting of the Biophysical                                 Society, Long Beach, CA

2005                    First Prize, Annual Research Day                                 Competition,                                                                                      Mildrel L. Schucker Travel Award,                                                            State University of New York, Downstate                                  Medical Center, Brooklyn, NY

2006                    Robert F. Furchgott Award for Excellence in                                 Research, State University of New York,                                            Downstate Medical Center, Brooklyn, NY

2008                    Research Fellowship Award, Rockefeller                                 University, New York, NY

2012                    Thematic Best Poster Award, American                                 Society of Biochemistry and Molecular                                 Biology

2012-2013       NIH Pathway to Independence Award (K99),                                  Mechanisms and Regulation of Translesion                                  DNA Polymerases, National Cancer Institute

2013-2016       NIH R00 Award, Mechanisms and                                   Regulation of Translesion DNA Polymerases                                     National Cancer Institute

2014-2017       DOD Breast Cancer Breakthrough Award                                   Identifying Compounds for Targeted Breast                                  Cancer Treatment and Prevention

2016                     New Investigator Award                                   Center for Translational Research,                                   Temple University                                                                                  Lewis Katz School of Medicine