Research laboratory of Tanaji Talele, PhD

About Tanaji Talele

Tanaji Talele received his B.S. degree in pharmacy from the University of Pune in 1992. He then went on to receive his M.S. (1994) and Ph.D. (1998) degrees from the University of Mumbai, both in Medicinal Chemistry. He completed his postdoctoral training in biochemistry/virology/peptide chemistry/organic chemistry at New Jersey Medical School, Louisiana State University, University of South Florida, and Moffitt Cancer Center (1999-2005). In 2005, Professor Talele joined the College of Pharmacy and Health Sciences at St. John’s University as an Assistant Professor of Medicinal Chemistry, where he was promoted to Associate Professor in 2009 and to full Professor in 2014. Principal research efforts in his group include the development of small molecule inhibitors of poly (ADP-ribose) polymerases (PARPs), histone deacetylases (HDACs), and Ser-Thr kinases for the treatment of cancer. His team was the first to develop PARP1 inhibitors with unique mechanism of action (i.e., allosteric retention of PARP1 on DNA breaks). His research combines tools from organic synthesis, structural biology, and molecular modeling. He has published 103 articles in peer-reviewed journals, including Science, Nature Cell Biology, and Journal of Medicinal Chemistry. Since 2016, he has been serving as an editorial advisory board member of the European Journal of Medicinal Chemistry. He also served as the Editor of Bioorganic Chemistry from 2018-2024. Since 2005, he has graduated 7 Ph.D. and 12 M.S. students in the field of medicinal chemistry and molecular modeling. Currently he is mentoring one postdoctoral fellow and two Ph. D. students.

Research page under construction

Current Research:

Dr. Tanaji Talele’s research interests are largely directed toward development of small molecule inhibitors of DNA damage repair processes as promising anticancer therapeutics. To achieve this goal, we are primarily targeting PARP1 enzyme that plays a key role in DNA damage repair. Our lab is also focusing on development of highly selective inhibitors for other PARP family members including PARP7, PARP10, and PARP14 to understand the role of these PARPs in DNA damage repair processes. In addition, these inhibitors will serve as novel class of anticancer therapeutics.

PARP1 Inhibitor and Biophysics

Our team is the first one to discover type I PARP-trapping inhibitors. The study published in Science 2020 shows the conversion of type III (prorelease from DNA breaks) inhibitor (veliparib) into type III (pro-retention on DNA breaks) inhibitor (UKTT-15). The study demonstrates the feasibility of developing small molecule PARPi with a novel mechanism of allosterically promoting PARP1 retention on DNA breaks. PARPi retention on DNA breaks has been shown to contribute to high efficacy of PARPi in the clinic. We are optimistic that our ongoing research in this area will identify novel class of PARPi with unique position in PARPi space.

Science 2020, 368(6486), eaax6367

PARP1 Inhibitor and Biophysics

Using the benzimidazole-4-carboxamide pharmacophore present in the first generation PARP1 inhibitor veliparib, a series of compounds was designed, synthesized, and evaluated as allosteric PARP1 inhibitors, with the premise that bulky substituents would engage the regulatory helical domain (HD) and thereby promote PARP1 retention on DNA breaks. These compounds highlight a unique way to trigger PARP1 retention on DNA breaks and open a path to unveil the pharmacological benefits of such inhibitors with novel properties.

Biochem. J. 2024, 481(6), 437-460.

PARP1 Inhibitor Development

Structure of a DHBF-3-one-7-carboxamide-based PARP1 inhibitor (magenta) bound to the multidomain PARP1 complex with damaged DNA. Three residues are shown (His862, Tyr896, and Glu988) to highlight the conserved H-Y-E PARP signature motif in the PARP1 catalytic domain (green).

J. Med. Chem. 2014, 57, 5579-5601

J. Med. Chem. 2019, 62, 5330-5357

Nanomolar PARP1 inhibitors based on benzodioxine-5-carboxamide scaffold.

Bioorg. Chem. 2020, 102, 104075

Area of Expertise

Medicinal Chemistry

Computer-Aided Drug Design

Biochemical assays

In vitro ADME

News and Highlights

October 2021: The Talele group welcomes new postdoctoral fellow Manisha Patil, PhD to the lab.

November 2022: The Talele group welcomes new postdoctoral fellow Sonal Bhandari, PhD to the lab.

January 2023: The Talele group welcomes new MS student Ugochi Adiele to the lab.

March 2023: The Talele group welcomes new PhD student Abosede Salami to the lab.

July 2023: The Talele group welcomes new postdoctoral fellow Ramaraju Andhavaram, PhD to the lab.

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