Published December 22, 2020
Four students in the MD-PhD Program have received prestigious fellowships from the National Institutes of Health (NIH) in 2020.
The Ruth L. Kirschstein Individual Predoctoral NRSA for MD/PhD and other Dual Degree Fellowships (F30) is intended to enhance research and clinical training of promising predoctoral students who are matriculated in a combined MD-PhD training program and plan to pursue careers as physician-scientists.
Clayton Brady, a fourth-year student from Fairport, New York, works in the lab of Mark D. Parker, PhD, associate professor of physiology and biophysics.
His project, “Investigating the Role of NBCe1-B in Renal and Cardiac Acid-Base Handling,” received an award of $204,175, administered over the course of five years.
“Acid-base balance throughout the body is extremely well regulated and maintaining a blood pH near 7.4 is really an essential component of health,” Brady says. “However, what we are starting to realize is the processes that regulate pH might actually contribute to the development of disease themselves.”
“For example, the kidney responds to an acidic blood pH by increasing the excretion of acid in the urine, but over time this adaptation may in fact cause kidney damage,” he notes. “In the heart, a decrease in pH can impair its normal contractile function, which is initially compensated for through increases in the transport of ions that stimulate contractions, but if this compensatory state continues it can lead to the development of heart failure.”
The goal of Brady’s project is to better understand how these maladaptations occur and focuses specifically on the role of the protein NBCe1-B, which is a cellular acid-base transporter suggested to be involved in the responses of both the kidney and heart to acidosis.
“Instead of just treating the acidosis itself, my hope is that by gaining a better understanding of how the kidney and heart respond to acidosis we will be able to someday develop therapies that prevent these maladaptive changes directly,” he says.
Brady says he was elated to learn he had received an F30 fellowship, noting “its incredibly humbling to know others believe my ideas are worth pursuing.”
“I hope to make a career as a physician-scientist, splitting my time between seeing patients and running a research laboratory, which will really only be possible with the support of funding from institutions such as the NIH,” he says. “So simply going through the process of writing and submitting the proposal I think gave me invaluable experience in learning what it takes to be a successful scientist.”
Brady remembers meeting Parker for the first time during his interview for the MD-PhD Program.
“He immediately twisted his computer monitor toward my chair so he could show me the results of a previous day’s experiment,” he recalls. “His enthusiasm for his work really led me to seek a position in his lab.”
“Dr. Parker maintains a smaller research group compared to some other labs and this fit well with my personality as I have benefited greatly from being able to approach him with little or no notice to discuss not only research, but really any sort of concern I might have that day,” Brady says. “I always come out of such conversations more motivated than before and that ability to inspire confidence is something I hope to emulate throughout my career.”
Parker says it is a testament to Brady’s academic prowess and clinical promise that his application was awarded on first submission.
“Clayton shares my research interests and is set on a career in nephrology,” he says. “He is very skilled, thoughtful and driven in his approach to lab work. I have no doubt that Clayton has an extremely bright future ahead of him.”
Since Brady is investigating aspects of cardiac function as well as kidney function, he says he has been fortunate to have the opportunity to collaborate with Jennifer K. Lang, MD, assistant professor of medicine in the Division of Cardiovascular Medicine, who leads a cardiac-focused research lab at UB’s Clinical and Translational Research Center (CTRC).
“It is because of Dr. Lang’s expertise and the resources provided by her lab that we have been able to for the first time investigate the role of NBCe1-B in cardiac function in vivo, which is a central aspect of my proposal,” Brady says. “Dr. Lang currently practices at the Buffalo VA Medical Center and has been gracious enough to let me shadow her, which has allowed me to maintain a connection to clinical medicine during my graduate school years.”
Brady has also shadowed Elie R. Chemaly, MD, PhD, clinical assistant professor of medicine in the Division of Nephrology, who is a nephrologist at Roswell Park Comprehensive Cancer Center.
“Dr. Chemaly is also involved with basic science research at the CTRC and was very helpful in developing the foundations of the proposal,” Brady says.
Elliot Kramer, a New York City native, is a fifth-year student working in the lab of Scott I. Abrams, PhD, professor of oncology in the Department of Immunology at Roswell Park Comprehensive Cancer Center.
His project, “The Wnt-IRF8 Axis: A Novel Regulator of Myeloid-Derived Suppressor Cell Biology,” received an award of $161,690, administered over the course of four years.
“The main thing that attracted me to UB’s MD-PhD program was the opportunity to work with exceptional mentors in an innovative research environment and gain clinical experience within Buffalo’s diverse hospital system,” he says. “I had the opportunity to speak with many research scientists at UB during my application process and I was very impressed with their work. I saw an excellent opportunity to pursue translational research in tumor immunology which was, and continues to be, of great interest to me.”
“Cancer is a devastating disease that affects the lives of over a million people in the United States every year. While treatments are steadily improving, hundreds of thousands still die annually, so it is essential to come up with new strategies to treat cancer,” Kramer says. “In the past few decades of research, it has become increasingly clear how important the body’s own immune system is in fighting cancer. That understanding has led to a new class of drugs called immunotherapies, which stimulate the immune system to do just that.”
One way that cancer cells resist immunotherapy is by recruiting myeloid-derived suppressor cells (MDSCs) to the tumor in overwhelming numbers.
“Therefore combining immunotherapy with a targeted inhibitor of MDSCs, potentially identified through my work, could overcome that resistance and increase the amount of people who do respond to immunotherapies,” Kramer notes.
“The main goal of my research is to understand how chemical signals produced by cancer cells cause the immune system to be weakened, hampering the ability of white blood cells to destroy the tumor,” he says.
“My work focuses on the signaling pathways within MDSCs that affect their growth and immunosuppressive function. Specifically, I am studying the interaction between two proteins, beta-catenin and interferon regulatory factor 8 (IRF8), which are thought to inhibit the activity of MDSCs when activated,” Kramer adds. “The goal being to identify drugs that can activate that signaling pathway, and then combining those drugs with existing immunotherapies to improve their efficacy in controlling tumor growth.”
Kramer notes that Abrams, his mentor, is a highly accomplished researcher by any measure.
“He has published numerous papers in the field of tumor immunology and has held several high-level faculty appointments during his time at Roswell Park, but most of all he is a skilled and compassionate mentor,” he says.
“Dr. Abrams has an impressive understanding of the scientific process and is truly skilled in communicating his ideas through scientific writing. For him, it’s not enough to provide general advice regarding his students’ research, instead he makes the time to have in-depth discussions and listens as much as he offers guidance,” Kramer adds.
For his part, Abrams says Kramer is “highly driven and passionate about biomedical research.”
“Elliot is a strong critical thinker. His ideas are creative and I believe will fill important gaps in our understanding of myeloid-tumor biology, which is the basis of his proposal,” he says.
Yuhao (Tom) Shi’s project, “Mechanisms of Acquired Resistance to PD-L1-Targeted Therapy in Cancer,” received an award of $62,044, administered over the course of two years.
Shi is a sixth-year student who works in the lab of John Ebos, PhD, associate professor of oncology in the Department of Cancer Genetics and Genomics at Roswell Park Comprehensive Cancer Center.
Shi and his family immigrated to the United States from China when he was 8 years old and he grew up in the suburbs of Albany, New York.
“My father is a scientist and a professor at Albany College of Pharmacy and Health Sciences and I think he helped foster a lot of my initial interests in pursuing science and medicine as a career,” Shi says.
One institution in particular stood out to Shi when he was investigating MD-PhD programs.
“I was very interested in cancer biology when applying to programs and the infrastructure and the faculty at Roswell Park Comprehensive Cancer Center was definitely a major part of my decision,” Shi says. “I also felt that the students and faculty in the program were very supportive of each other.”
“Dr. Ebos has been incredibly supportive as a mentor in the application of this fellowship. We worked very closely in the writing process and development of ideas,” he says. “He is extremely helpful when it comes to experimental design, interpreting data and understanding the literature. He’s a great motivator in the lab for those days when science gets tough and an advocator for many trainees at Roswell.”
Shi says he also worked closely with Scott I. Abrams, PhD, and Igor Puzanov, MD, professor of medicine, on his fellowship application and both have been very supportive of his training.
Ebos says that Shi “is an exceptional student” who is “both gifted and incredibly hard working.”
“Tom is one of the most committed students I have encountered in my career and his success in obtaining an F30 award is because of this dedication,” he says. “Tom has independently crafted his thesis ideas and driven the innovation forward with exciting experimental concepts, all of which have resulted in several highly novel new ideas for the field of immunotherapy and drug resistance.”
“One of Tom’s strongest attributes is in his ability to communicate complex ideas to audiences of all levels, a skill he has honed by giving multiple seminar and poster presentations at Roswell and at international conferences,” Ebos adds.
Ebos says Shi has dedicated himself to translational questions highly relevant to what patients are experiencing today.
“His clinical background and training has allowed him to bridge the gap between basic research and the most pertinent questions being asked (and tested) in clinical trials today.”
Shi’s research focus involves immune checkpoint therapy, a treatment rapidly gaining approval in the first- and second-line setting for several cancer types, in multiple cancer stages.
The premise of his F30 project is to understand mechanisms of resistance to cancer immunotherapy or immune checkpoint inhibitors.
“These drugs have been a breakthrough in oncology. For many patients treatment initially works, but after months and sometimes years, patients can relapse,” Shi says. “We hope to understand why this can happen and to develop new approaches after therapy fails.”
“Currently, in the U.S. and worldwide, immune checkpoint inhibitors are approved for many cancer disease sites with more clinical trials testing their use in new settings,” he adds. “Understanding why treatment can fail and how to approach treatment failure will be increasingly important.”
Michael Weaver, a native of Mount Laurel, New Jersey, is a sixth-year student working in the lab of M. Laura Feltri, MD, professor of biochemistry and neurology and co-director of the Hunter James Kelly Research Institute.
His one-year project, “Strn3 is a Novel Rac1 Effector in Schwann Cells,” received an award of $31,213.
“Our laboratory studies the cells that produce a substance called myelin, which forms an insulating fatty sheath around the nerves in our brain, spinal cord and throughout the rest of our body (peripheral nerves),” Weaver says.
These cells are broadly known as myelinating glia and the process of myelin formation is called myelination. Myelin is the substance that breaks down in diseases such as multiple sclerosis and Krabbe disease.
Myelin is also very important for regeneration following damage such as stroke and traumatic injury to the brain, spinal cord, or peripheral nerves.
“Specifically, we study the developmental aspects of myelin and how it is damaged with the goal of eventually facilitating the creation of new therapeutic strategies,” Weaver says. “My project investigates a family of proteins called the striatins, which were not previously studied in myelinating glia.”
“Our lab has previously demonstrated that Rac1 is critical for the myelination of peripheral nerves. Following the lead from this screen, we investigated further and found that the striatins are essential for the myelination of peripheral nerves,” he adds. “In addition, we have preliminary evidence that the striatins could be important for myelination in the brain and spinal cord.”
Weaver says Feltri excels in skills such as critical thinking, creativity and grantsmanship that are essential qualities for a scientist at her career level.
“Dr. Feltri gives us the independence needed to make our projects our own, but always keeps an open door to answer questions and help steer us when we need guidance,” he says. “She also sees us and treats us as human beings, each with our unique talents, challenges, needs and desires, in and out of the lab.”
“She wants us all to have a work-life balance while still excelling in our career goals, which is certainly not an easy task in our profession. She listens to us and remembers who we are and what our life is like outside of the lab,” Weaver says. “Just the other day, Dr. Feltri proclaimed, ‘People are the best part of science!’”
Feltri says Weaver is very motivated by research in the laboratory and works extremely hard.
“He also has an impressive background and knowledge in research for a person at his career stage, due to his extensive work in excellent laboratories as an undergraduate,” she says. “All this is evident at the bench, where he could produce good preliminary data for his application, and in his biosketch. I believe that all these things contributed to sending an appealing application.”
Weaver is also grateful for his thesis committee members of Yungki Park, PhD, assistant professor of biochemistry; Stylianos Andreadis, PhD, professor of biomedical engineering; and Fraser J. Sim, PhD, associate professor of pharmacology and toxicology and director of the neuroscience program.
“Each of them are extremely talented scientists with their own unique set of skills and together they make a stellar mentorship team for my project,” he says.
Weaver also wants to make sure to keep up his clinical skills throughout his work on a doctoral degree.
To that end, he works with Nicholas J. Silvestri, MD, clinical associate professor of neurology, in his clinic once a month.
“Dr. Silvestri has been a superb mentor since early on in my program and I hope to rely on his valuable guidance and insight in the coming years when I go back to medical school and eventually begin applying to research residencies,” Weaver says.