Since pathology class in medical school in Nepal, Sravanti Rangaraju, MBBS, this year’s George and Sarah Jane Fisher Young Investigator Award recipient, has found studying peripheral blood smears intriguing.

“When you look at blood cells under a microscope, you can get clues to several diagnoses just based on that,” said Dr. Rangaraju, a third-year hematology oncology fellow at Indiana University School of Medicine.

During her internship at the Northern Railway Central Hospital in India, she cared for a patient who was presumed to have tuberculosis due to enlarged lymph nodes, but actually had lymphoma.

“Through residency, I was interested in non-malignant hematology. I wanted to treat and workup anemias and blood clotting disorders. That completely changed when I entered fellowship because my first rotation was on the inpatient leukemia service. I was completely blown away by the disease biology of leukemia.”

Now Dr. Rangaraju is set on developing more effective treatments for patients with leukemia, especially for older patients who may not be able to tolerate aggressive chemotherapy-based treatments.

“There is a need to find less aggressive treatments for these patients,” Dr. Rangaraju said. “We need to create more effective treatments that can keep the disease at bay for a longer period, while maintaining an acceptable quality of life for our patients.”

Since arriving at IU, her research has focused on treating resistant leukemias.

“Acute myeloid leukemia is my specific area of interest,” Dr. Rangaraju said. “It affects mainly patients over 65 years of age. At that age group, they’re not always able to tolerate a lot of aggressive treatments, so we’re limited in what we can do.”

Currently, the standard of care is chemotherapy and in some cases a bone marrow transplant, which can be difficult for many patients to tolerate if they have other medical problems, she said.

One of the drugs she and other colleagues are studying at IU is bortezomib, a proteasome inhibitor that is used to treat multiple myeloma. This drug class works by blocking the protein degrading machinery of cells, which leads to accumulation of toxic proteins inside the cell and ultimately cell death.

“What I’m looking at is the combination of a proteasome inhibitor with a FLT3 inhibitor to treat AML,” Dr. Rangaraju said. “FLT3 is a cell signaling molecule which can be overexpressed in certain kinds of leukemia like FLT3-mutated AML, leading to a survival advantage of these cells. FLT3 inhibitors can block this cell signaling and kill leukemia cells.”

Currently, she and her mentor, H. Scott Boswell, MD, professor of medicine at IU School of Medicine and a researcher at Indiana University Melvin and Bren Simon Comprehensive Cancer Center, are working on the Big Ten Cancer Research Consortium study, BTCRC-HEM17-092, a phase I/II study augmenting the action of TAK-659 a FLT3/Syk inhibitor in relapsed/refractory AML by adding the proteasome inhibitor Ixazomib. They are investigating the safety, tolerability, and maximum tolerated dose of this combined therapy and will analyze samples from participants to understand the mechanism of action.

Dr. Rangaraju, who currently serves as chief fellow, distributes much of her time on the leukemia service, bone marrow transplant service, clinics with faculty, laboratory work, and administrative responsibilities.

She’s grateful to her mentors, including Dr. Boswell; Larry Cripe, MD, associate professor of medicine, IU School of Medicine and IU Simon Comprehensive Cancer Center; Edmund “Ned” Waller, MD, PhD, FACP, professor of medicine, pathology, hematology and medical oncology, Emory University School of Medicine; Heiko Konig, MD, PhD, assistant professor of medicine, IU School of Medicine and IU Simon Comprehensive Cancer Center; and her brother, Srikant Rangaraju, MBBS, associate professor of neurology, Emory University School of Medicine, who have taught her to think critically and navigate a career in research and academia.

“I think it’s important to pick up on things as you go from everyone you work with because everybody around you has something to teach you,” Dr. Rangaraju said. “I also learned a tremendous amount from patients, especially in terms of how they cope with their disease.”

She said she is grateful to be recognized this year with the George and Sarah Jane Fisher Young Investigator Award. The award honors Indiana University oncology fellows and faculty members who made significant contributions to clinical or basic science research conducted in cooperation with Hoosier Cancer Research Network. The award was established in 2011 through the support of William B. Fisher, MD, and the George and Sarah Jane Fisher Fund to stimulate the work of the next generation of cancer researchers.

“It’s very humbling,” Dr. Rangaraju said. “I’d like to thank Dr. Fisher and the entire Hoosier Cancer Research Network selection committee for being able to support this award for fellows. It means a lot to get the recognition as well as the extra motivation to support grant applications. The award has had a lasting impact on a lot of fellows who have graduated.”

Dr. Rangaraju said that she values the validation of her work, especially when there are times in the research and development process when investigators confront challenges. “Sometimes you feel like you’re hitting a wall, be it in terms of research results or financial support. The award gives you the encouragement to keep going,” she said.

After completing medical school at the Manipal College of Medical Science in Nepal, Dr. Rangaraju completed her postdoctoral research fellowship in transplant immunology at Emory University, with a research focus on graft-versus-host disease. She then completed her residency in internal medicine at the University of Minnesota with an emphasis on global health, and then arrived at Indiana University for her hematology oncology fellowship.

Upon completing her fellowship this spring, Dr. Rangaraju will join the leukemia division at University of Alabama at Birmingham School of Medicine.

“My goal is to pursue a translational research career, where I have a strong clinical presence and collaborate with basic laboratory scientists,” Dr. Rangaraju said. “I want to develop hypothesis-driven combination therapies for leukemia and push that work into early phase clinical trials. Ultimately, I want to bring the best treatments to our patients and help them manage their cancer.”

— Story by Angie Antonopoulos

About Hoosier Cancer Research Network:

Hoosier Cancer Research Network (formerly known as Hoosier Oncology Group) conducts innovative cancer research in collaboration with academic and community physicians and scientists across the United States. The organization provides comprehensive clinical trial management and support, from conception through publication. Created in 1984 as a program of the Walther Cancer Institute, Hoosier Cancer Research Network became an independent nonprofit clinical research organization in 2007. Since its founding, Hoosier Cancer Research Network has conducted more than 210 trials in a variety of cancer types and supportive care, resulting in more than 350 publications. More than 8,500 subjects have participated in Hoosier Cancer Research Network clinical trials.