At first glance the colorful image (inset and on front cover) may resemble a stained-glass window on a great cathedral, but it depicts far more than meets the eye. This image, the winning entry in an Art of Cancer Research Contest held as part of the OSUCCC – James’ 2021 Annual Scientific Meeting, shows individual patient-derived organoids (PDOs) arranged in a circular pattern as a stylistic interpretation of novel cancer therapy targets that these PDO models help uncover. It’s the work of Vijaya Bharti, PhD, MS, a postdoctoral researcher in the Department of Pathology at the Ohio State College of Medicine whose research focuses generally on translational therapeutics and specifically on developing effective therapies for breast cancer, melanoma and other malignancies.
Her studies utilize patient-derived models such as PDOs, as well as immunocompetent mouse models. “My current focus is on developing combination therapies and investigating the effect of drugs on the tumor immune microenvironment (area surrounding the tumor),” says Bharti, whose mentors are Anna Vilgelm, MD, PhD, and Ramesh Ganju, PhD, both of the Department of Pathology and the OSUCCC – James. “The goal is to find ways to mobilize tumor-targeting immune cells into the tumor to facilitate a ‘hot’ immune tumor microenvironment. We want to determine if we can harness chemokines (proteins) produced by tumor cells as a stress response to drug treatment to augment the efficacy of immunotherapy.”
She explains that organoids are tiny, self-organized, threedimensional tissue cultures derived from patient tumor cells. The organoids in her winning image – captured via fluorescence microscopes – were derived from 19 patients with melanoma. After being treated with drugs and drug combinations, the organoids were stained with green fluorescent dye to identify live cells, red fluorescent dye to identify dying cells, and a blue DNA dye, and then arranged circularly to complete the image, which is part of a study that has been submitted for publication in a scientific journal.
Bharti was born and raised in Bihar Sahrif, India, and earned her undergraduate degree (biology), master’s degree (biomedical sciences) and PhD (biotechnology) in that nation before becoming a postdoctoral researcher in the Vilgelm lab at Vanderbilt University in 2019. “Working in cancer drug discovery in Dr. Vilgelm’s lab honed my skills and heightened my interest in translational cancer therapeutics. I moved with Dr. Vilgelm when she came to Ohio State,” says Bharti, whose husband, Amrendra Kumar, PhD, is also a research scientist in the Pathology Department.
Bharti says she was inspired to become a cancer researcher seeking new therapies during her PhD studies when she worked with samples/specimens collected from patients at cancer hospitals. “I became concerned to see a large number of relapse cases, including my mother, despite several advances in therapy and surgery. My research has found several drugs that block cancer progression can also induce the secretion of small proteins known as chemokines that attract immune cells to the sight of cancers. “On the other hand, immunotherapies have shown to have profound success in a subset of cancer patients; however, more work is required. With combination therapy, we expect to target more anticancer immune cells to the tumors and eliminate them.” She also has received a postdoctoral fellowship award funded by Pelotonia, the annual grassroots cycling event that raises money for cancer research at Ohio State. Under the guidance of Vilgelm and Ganju, her fellowship project is using a laboratory model of metastatic breast cancer to test whether combining a drug called abemaciclib – which inhibits a protein that is overactive in this disease – with an infusion of therapeutic natural killer (NK) immune cells will help eliminate tumors. “The Pelotonia fellowship is vital to my career development,” Bharti says. “I see it as a major step toward an independent research career in translational science.”