Priyamvada Rai, Ph.D.
Associate Professor of Medicine
Description of Research
Dr. Rai's major research interests center around the effect of reactive oxygen species (ROS) levels and oxidative DNA damage on tumor suppressor pathways. Many tumors are characterized by high levels of oxidative stress due to elevated metabolic activity, impaired mitochondrial function and ROS production through hyperactivation of oncogenic signaling. A number of chemotherapeutics have been developed to exploit this situation by selectively killing cancer cells via enhancement of existing oxidative stress and DNA damage. However, some aggressive types of cancers are resistant to such treatments and in many cases, chemoresistance has been linked to elevated levels of cellular redox-protective proteins. These redox-protective proteins, being structurally small and well-defined, can serve as potential targets for therapeutics that selectively destroy transformed but not normal cells. Additionally, the ability of this class of proteins in protecting against specific stress responses also renders them valuable prognostic or diagnostic markers, allowing for individualized treatment regimens.
Accordingly, Dr. Rai is interested in studying the mechanisms by which cancer cells combat oxidative stress and utilize redox and DNA repair pathways to evade tumor suppressor responses. A major focus of her studies is to develop molecular strategies to reactivate or enhance tumor suppressor pathways such as senescence and apoptosis in cancer cells, through modulation of cellular redox status and DNA repair mechanisms.
Dr. Rai is currently focusing on studying the pro-tumorigenic contributions of two functionally distinct redox-protective proteins, thioredoxin-1 (TRX1), a thiol protein, and human MutT Homolog (MTH1), the major mammalian 8-oxoGTPase. TRX is found at elevated levels in advanced prostate cancer whereas MTH1 expression is enhanced in oncogenic RAS-sustaining lung tumors. In order to assess their role in facilitating tumor progression and chemoresistance, Dr. Rai has developed gain-of-function/loss-of-function systems for use in cell and animal models. Her research encompasses a critically understudied area, namely the segregation of pleiotropic functions of ROS at a molecular level so their effect on tumor versus normal cells can be studied under specific contexts. The eventual goal of her research is to leverage the experimental findings from her laboratory towards optimizing existing treatment regimens and/or identifying therapeutic targets that can be utilized by oncologists to successfully treat cancer patients. To this end, Dr. Rai has ongoing collaborations with UM/SCCC clinicians in order to validate her findings in human-derived tumor tissue. Her research on the role of MTH1 in promoting tumor growth and progression in nonsmall cell lung carcinoma (NSCLC) is being done in collaboration with Dr. David Robbins and Dr. Dao Nguyen (Molecular Oncology/Surgery). Her study on the role of TRX1 in promoting outgrowth of ADT-resistant prostate cancer cells is being done in collaboration with Dr. Carlos Perez-Stable (Medicine) and Dr. Merce Jorda (Pathology).
- Developed cell-physiologic models to isolate the role of oxidative DNA damage from pleiotropic oxidant effects in tumor suppressor pathway activation and induction of cellular senescence.
- Was the first to demonstrate that inhibiting MTH1, the major nucleotide pool-sanitizing enzyme, is a critical pathway for inducing tumor-suppressive DNA double-strand breaks and oncogene-induced senescence, particularly in RAS-driven tumor cells.
- Demonstrated novel contributions from a senescent microenvironment in promoting outgrowth of androgen-refractory prostate cancer cell subpopulations; developed an innovative method for generating androgen-refractory cell subpopulations.
- Dr. Rai’s research is funded by an NIH/NCI R01 award and a New Investigator Research award from the NCI-designated Bankhead-Coley Florida Biomed Research program.
Selected Cancer-Related Publications
- Burton DG, Giribaldi MG, Munoz A, Halvorsen K, Patel A, Jorda M, Perez-Stable C, Rai P. Androgen deprivation-induced senescence promotes outgrowth of androgen-refractory prostate cancer cells. PLoS One 8:e68003,2013 Read more »
- Rai P, Rao RN, Chakraborthy SB. Caecal lymphangioma: a rare cause of gastrointestinal blood loss. BMJ Case Rep 2013:,2013 Read more »
- Rai P. Human Mut T Homolog 1 (MTH1): A roadblock for the tumor-suppressive effects of oncogenic RAS-induced ROS. Small Gtpases 3:120-5,2012 Read more »
- Rai P, Young JJ, Burton DG, Giribaldi MG, Onder TT, Weinberg RA. Enhanced elimination of oxidized guanine nucleotides inhibits oncogenic RAS-induced DNA damage and premature senescence. Oncogene 30:1489-96,2011 Read more »
- Rai P. Oxidation in the nucleotide pool,the DNA damage response and cellular senescence: Defective bricks build a defective house. Mutat Res 703:71-81,2010 Read more »
Collaborating in the Multidisciplinary Research Program(s):