David A. Boothman
Sidney and Lois Eskenazi Professor of Hematology-Oncology
Dr. Boothman grew up in Detroit, Michigan, and earned his B.S. at the University of Michigan-Ann Arbor. He did his graduate work in microbiology and immunology at the University of Miami Medical School, where he received his Ph.D. under the mentorship of Dr. Sheldon Greer. His research focused on the biochemistry and pharmacology of anticancer drugs, specifically 5-fluoro-deoxycytidine derivatives.
He did postdoctoral research at the Dana-Farber Cancer Institute of Harvard Medical School with Dr. Arthur B. Pardee. There, he investigated changes in several aspects of cancer cells before and after cell stress: cell cycle checkpoint regulation, molecular biology, and gene expression. His studies on β-lapachone as a radiosensitizer and DNA repair inhibitor began at this time. Dr. Boothman also discovered and cloned the first proteins and transcripts induced by ionizing radiation (IR).
In 1990, Dr. Boothman became Assistant Professor at the University of Michigan-Ann Arbor and continued his investigations of x-ray-inducible proteins (Boothman et al., Cancer Research, 1988), and x-ray-inducible transcripts leading to proteins (Boothman et al., PNAS, 2000). He discovered xip8 (clusterin) and its induction by super-low levels of IR exposure. Dr. Boothman then joined the faculty in the Department of Human Oncology at the University of Wisconsin-Madison, where he rose to Associate Professor with tenure and became the Vice Chairman of Radiation Oncology, and Division Head of Molecular Radiation Oncology.
In 1998, Dr. Boothman accepted an Endowed Professorship at Case Western Reserve University and became heavily involved in the Cancer Center. In 2000, he became the Associate Director for Basic Science and headed the research effort in the Cancer Center’s Wolstein Research Building.
In 2005, Dr. Boothman and his close colleague Dr. Jinming Gao moved to the University of Texas Southwestern Medical Center to start the Cell Stress and Cancer Nanomedicine Program.
In 2017, Dr. Boothman moved to the Indiana University School of Medicine where he accepted the position of Professor of Biochemistry and Molecular Biology, and became the Sid and Lois Eskenazi Chair in Cancer Research, and the Associate Director of Translational Researchin the Simon Cancer Center.
Dr. Boothman has trained 16 Ph.D. students, two M.D./Ph.D. students, and more than 40 postdoctoral fellows and residents, who enjoy positions around the nation and in seven different countries and in various aspects of scientific research.
Titles & Appointments
- Professor of Biochemistry & Molecular Biology
The overall mission of the Boothman laboratory is to understand and exploit cell stress responses in cancer versus normal cells. There are three ongoing projects in the laboratory focused on: i) DNA double strand break (DSB) repair and the specific roles of RNA transcription termination factors in the regulation and control of RNA Pol II-mediated R-loop formation, and the impact of loss of RNA termination factors (e.g., RPRD1B, RPRD1A and XRN2) on DSB repair and sensitivities of cancers to DNA damaging agents and DNA repair inhibitors; ii) EMT, migration and metastasis and the influences of, or changes in, metabolism during TGFß1-driven EMT; and iii) exploiting NQO1 bioactivatable drugs for improved therapy of cancers that have elevated levels of NAD(P)H:quinone oxidoreductase 1 (NQO1), including cancers of the lung (NSCLC), pancreas (PDA), breast (including TNBC), and prostate. Dr. Boothman has identified several cell stress response pathways, such as Ku70 binding protein #5 (kub5/hera, K-H/RPRD1B) XRN2 or RPRD1A loss, the ATM-IGF-1-sCLU pathway, and the NQO1 bioreduction pathway, with which to exploit using unique and novel strategies. His lab has developed mechanisms and/or drugs to exploit these for improved therapy of NSCLC, pancreatic, prostate, breast, and colon cancers. Recent systems have been derived for the RPRD1B/Kub5/Hera (K/H) gene in cancer cell lines, but where CDK1, BRCA1/2, PARP1 or Artemis have been modified. These cell and animal systems are ideal for mechanistic studies. In his capacity as an External Advisory Board member, he will consult on the expression studies of NRF2 and its regulation of downstream genes, as well as using changes to explore therapeutic strategies for NSCLC
Dr. Boothman has been developing NQO1 bioactivatable-specific drugs for the past 15 years, and has moved one version of the drug (ARQ761, ß-lapachone) into three clinical trials at UT Southwestern against various cancers, including solid cancers, e.g., breast (TNBC), NSCLC, PDAs and bladder cancers. He has developed numerous isogenic systems of cancer cells (in lung, breast, pancreatic, and prostate cancers) that are deficient or knocked down for NQO1 expression plus derivative pooled and cloned populations where NQO1 expression has been restored (with siRNA-resistance cDNAs or re-expressed in clones knocked down for NQO1 using 5’- UTR-specific sh/siRNAs).