Spotlight on OCASCR Scientist
Resham Bhattacharya, Ph.D.
Department of Obstetrics and Gynecology
University of Oklahoma Health Sciences Center
1. What is your lab’s long-term/big-picture research goal?
Our research is focused on investigating the basic and clinical translational aspects of molecular signaling in vascular pathologies and in gynecologic cancers, primarily ovarian and uterine cancer. Our long-standing interest in the biology of the gasotransmitter hydrogen-sulfide has resulted in clarification of protein modifications that regulate the maintenance of vascular function. We have discovered unique roles for the protein BMI1 that we have shown is required for maintenance of stemness and resistance to chemotherapy in cancer. In the aggressive and difficult to treat uterine carcinosarcoma, where there is currently no targeted therapy, we have identified the Tumor Growth Factor Beta pathway to be an important molecular target. Both of these bench projects have been translated into clinical trials at the OUHSC. Lastly, we have reported several other observations pertaining to mechanisms of cellular uptake, drug delivery, nanodesign and novel signaling. Our overall goal is to identify and establish new regulators of tumor progression and metastasis that can serve as therapeutic targets to effectively treat patients with gynecologic malignancies.
2. What is your training/scientific background?
I joined the faculty in the Department of Obstetrics and Gynecology at the University of Oklahoma Health Sciences Center (OUHSC) in July of 2013 and currently am an Associate Professor. Since the beginning of my research career, I have been interested in the biology of cancer. While working with Dr. Doris J. Beck at the Bowling Green State University, my graduate thesis focused on defining DNA repair pathways involved in regulating resistance to cisplatin. During my post-doctoral years at the Harvard Medical School, I focused on basic endothelial signaling and tumor angiogenesis. Later, while at the Mayo Clinic in Rochester, MN, I continued to work on tumor angiogenesis and started my own program in cancer biology. I am particularly focused on ovarian cancer signaling because understanding this would lead to better clinical-translational approaches.
3. What is the goal of your OCASCR project?
As cells grow and divide, their primary objective is to replicate accurately and by doing so maintain genomic integrity. However, cells are bombarded daily with intrinsic and extrinsic factors that cause DNA damage and threaten the integrity of dividing cells. Environmental carcinogens, including smoking, are major extrinsic factors that damage the DNA. If left unrepaired, these breaks can cause aberrant replication resulting in mutations leading to cancer. Cells have therefore developed mechanisms for alleviating DNA damage, ensuring sanctity of the cell cycle. These mechanisms are collectively known as the DNA damage response (DDR), which includes cellular checkpoints and DNA repair. These checkpoints are regulated by TP53 and the checkpoint kinases 1 and 2 (CHK1 and CHK2). However, in the majority of malignancies, TP53 is either mutated or deleted rendering cancer cells more reliant on the checkpoint kinases, suggesting that defects in checkpoint would lead to a defective DDR and cell death. This has made checkpoint signaling very attractive in cancer therapeutics, and CHK1 has emerged as a critical target. Our results indicate that KRCC1, a novel protein with unknown biology may play a role in the DDR via CHK1 and also inhibit DNA repair. Here we want to study how KRCC1 regulates the damage response and DNA repair using ovarian cancer as a model system.
4. How might your research impact diseases related to obesity or smoking?
Environmental carcinogens including smoking are major extrinsic factors that damage the DNA and cause breaks. If left unrepaired, these breaks can cause aberrant replication resulting in mutations leading to cancer. Hence investigating how novel proteins participate in preserving genomic integrity may have consequences in terms of cancer therapy.
5. What’s your most critical piece of research equipment in your lab? Why?
Probably the Clariostar from BMG Labtech because of its extreme flexibility in being able to measure absorbance, fluorescence and luminescence.
6. What’s your favorite scientific meeting to attend? Why?
The Gordon Research Conference on Mammalian DNA Repair and the Mayo Clinic Angiogenesis Symposium. Both of these meetings are attended by leading scientists in the field with similar research interests as mine, allowing meaningful scientific exchange, collaboration and networking.
7. What did we forget to ask?
I love and listen to a wide variety of music.