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Joann Sweasy, PhD

Ensign Professor Emeritus of Therapeutic Radiology
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About

Titles

Ensign Professor Emeritus of Therapeutic Radiology

Biography

I am an expert in the genetics, cell biology, mutagenesis and biochemistry of DNA repair and cancer and have been funded continuously by the NIH since 1994. A major focus of my laboratory is to understand how single nucleotide polymorphisms in DNA repair genes, including genes that function in homology directed repair (HDR), nonhomologous end-joining (NHEJ) and base excision repair (BER) in the germline and somatic tissues impact cancer risk and treatment. We have recently found that RAD51, DNA glycosylase, and POLB germline and somatic tumor variants exhibit functional phenotypes that lead to cellular transformation, genomic instability, and sensitivity or resistance to chemotherapies and ionizing radiation. We have also developed methods to monitor DNA damage in tissue including the presence of single and double strand breaks that lead to PARP activation and trapping. In addition to this, I have focused on determining the roles of DNA repair in a vertebrate organism and have concentrated my studies on mouse models of DNA repair variants. Using these models I have revealed critical roles for DNA repair in preventing the autoimmune disease of lupus. As Associate Director for Basic Research at the Yale Comprehensive Cancer Center, I oversee several pilot and internal grant competitions, am the Principal Investigator of the American Cancer Society Institutional Research Grant, and am currently leading the development of a Translational Research Core which is designed to link patient health records to biospecimens, genomics data, and a living tumor registry.

Appointments

Other Departments & Organizations

Education & Training

Postdoctoral Research Fellow
University of Washington, Seattle, WA (1993)
PhD
Rutgers University (1989)
Senior Staff Microbiologist
Merck and Company, Rahway, NJ (1989)
Graduate Research Fellow
Rutgers University,Piscataway, NJ (1989)
BA
Beaver College, Biology and Chemistry (1980)
Undergraduate Research Assistant,
Beaver College, Glenside, PA (1980)
Postdoctoral Fellow
University of Washington, Seattle, WA

Research

Overview

A major goal of the research conducted in my laboratory is to study the relationship between mutations and cancer. Therefore we concentrate our efforts on studying the mechanism of mutagenesis by a DNA polymerase, polymerase § (Pol §). We employ genetic screens to identify amino acid residues of Pol § that function in promoting the fidelity of DNA synthesis. The Pol § mutant proteins identified in these screens are then analyzed using kinetics to determine the mechanism(s) Pol § employs to synthesize DNA accurately.

We also study the cellular role of Pol § and have shown that Pol § participates in base excision repair and in the process of meiosis. We are pursuing these studies to determine how Pol § makes errors during base excision repair and to identify the role of Pol § in meiosis.Pol § IgG stains discrete foci on mouse chromosome homologs during prophase I of meiosis in mouse spermatocytes. Mouse spermatocytes in early prophase. A, B) Nucleus in late zygonema. Pol §-stained nuclei (red) are on the left; Pol § and Cor I-stained nuclei (white) on the right. C) Nucleus in mid-pachynema. Merged image of Pol § and Cor I-stained nucleus. D) Nucleus in late pachynema and proceeding into diplonema. Merged image of Pol § and Cor I-stained nucleus. Control experiments done in parallel with equivalent chromosomal spreads using preimmune serum or Pol §-depleted IgG fractions yielded no detectable staining (data not shown).

Medical Subject Headings (MeSH)

Carcinogenesis; DNA Repair; DNA Replication; Genetics; Mutagenesis; Radiation Oncology

Research at a Glance

Yale Co-Authors

Frequent collaborators of Joann Sweasy's published research.

Publications

2024

2020

2017

Academic Achievements & Community Involvement

  • honor

    Argall and Anna Hull Award

  • honor

    American Cancer Society Junior Faculty Research Award

  • honor

    Donaghue Investigator Award

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