Ameet Chimote, PhD
Research Associate, University of Cincinnati, Department of Internal Medicine, Division of Nephrology, Cincinnati, OH, USA
Connect with Ameet
Ameet is currently a Research Associate in Dr. Laura Conforti’s laboratory at the University of Cincinnati, where he studies the role of ion channels in T lymphocyte function, primarily in the context of solid tumors. He obtained his degree in Medicine from the University of Nagpur, India and completed his doctoral training where he studied ion transport physiology in disease causation under the guidance of Dr. Peter Lauf at Wright State University in Dayton Ohio. Subsequently, Ameet joined Dr. Conforti’s laboratory as a postdoctoral fellow where he optimized the methodology for isolating tumor infiltrating lymphocytes from head and neck squamous cell tumors and developed various flow cytometry and microscopy based assays to detect ion channel function in blood and biopsy specimens from cancer patients. Ameet then transitioned to the position of Research Associate in Dr. Conforti’s laboratory in 2015 and is currently continuing with his translational research. In addition to his research responsibilities in Dr. Conforti’s laboratory, Ameet is also passionate about mentoring young STEM students in the laboratory and about science communication and outreach.
Learn about Ameet’s research
Title: Defects in potassium channels contribute to reduced immune surveillance in cancers
- Understanding the physiological role of Kv1.3 and KCa3.1 channels in T cell function and learn how their defective function in cancer T cells can lead to decreased immune anti-tumor response.
- Learn about the various experimental methodologies and functional assays to assess T cell function.
Harnessing the immune system has emerged as a powerful therapeutic strategy in oncology. However, the limited ability of cytotoxic CD8+ T cells to infiltrate solid tumors presents a major roadblock to develop effective immunotherapy. Cytotoxic CD8+ T cells, in fact, have to infiltrate solid tumors, attack and kill cancer cells in order to provide an effective antitumor response. CD8+ T cell effector functions depend on Ca2+ influx into the T cell, which is controlled by two potassium (K+) channels: the voltage-dependent Kv1.3 and the Ca2+-activated KCa3.1. Our laboratory studies the contribution of these channels to T cell effector functions in patients with head and neck squamous cell carcinoma (HNSCC). We recently reported a decreased Kv1.3 function accompanied by a decrease in Ca2+ influx in tumor infiltrating lymphocytes (TILs) isolated from HNSCC patients. Furthermore, CD8+ TILs expressing high Kv1.3 levels and showing increased cell proliferation and cytotoxicity preferentially accumulated in the stroma. We also reported a role for K+ channels in regulating CD8+ T cell infiltration in tumors. Various intratumoral factors, especially the nucleoside adenosine limit the accumulation of TILs. We analyzed the migration of CD8+ T cells from HNSCC patients using a 3D chemotaxis assay and observed that adenosine inhibited the chemotaxis of CD8+ T cells from HNSCC patients to a greater degree than CD8+ T cells from healthy individuals. This increased sensitivity of HNSCC CD8+ T cells to adenosine correlated with their inability to infiltrate the tumor and was due to a decrease in KCa3.1 activity. Thus, our data indicate that defects in the K+ channels in T cells limit their effector functions and migration into the tumors, thereby contributing to the reduced anti-tumor immune response. Positive modulators of these channels could improve cancer immune surveillance, thus potentially opening new avenues for cancer immunotherapy.
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Get to know Ameet:
Why did you choose cancer research?
I have studied medicine and worked as a doctor in India and I have seen from close (and personal) quarters how this disease can affect individuals and families. I have always been motivated to do patient-centric translational research which has an impact on understanding a disease process and which can lead to development of therapeutics to treat that disease. I want to understand the complexities of how cancerous tumors grow, I want to know why the immune cells cannot attack and destroy the solid tumors and I want to know what we can do to empower the immune cells to attack and destroy the cancer cells.
What motivates you to succeed in your field?
A challenge: For me, it gives me an opportunity to read in depth, come up with strategies to troubleshoot and often come up with “out of the box solutions” to solve the problem. I also love to master new techniques and adapt them to answer research questions.
Optimism. Even when experiments do not work, I do not lose hope. I keep troubleshooting until I am sure if the negative result is a true negative result or due to a technical shortcoming. I will then try to design the correct meaningful alternative experiment that will provide me with the required answer
Describe yourself with 3 words:
Honest, hardworking, humble.
On your days off, what do you do?
Relax, watch TV, gardening, testing new recipes in my kitchen!
What is outreach/STEM to you?
Working in an Academic University that encourages science and research, I have had the good fortune to mentor several young undergraduate students in our laboratory. It is very important to teach the new generation to be inquisitive, think critically, learn problem-solving approaches and I think STEM education is important to educate individuals in this matter. Furthermore, outreach of the work that we do in our research laboratories helps create awareness on how basic research is essential to bring about some breakthroughs in the field of medicine. I am also a big advocate that opportunities in research in the STEM field should be accessible widely and made available to everyone irrespective of where they come from and who they are. To encourage more diverse and deserving minds to pursue careers in STEM, I feel that there should not just be more outreach, but also more funding.
“Be fearless, learn from your mistakes and have fun”—this advice from my idol, the great Julia Child continues to inspire me in the kitchen and in the lab!
How do you relax after a hard day of work?
Nothing is as therapeutic as stirring a big pot of curry.
If you could convince everyone in the world to do one thing at one point in time, what would that thing be?
Be kind to one another and treat everyone with respect
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