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Faculty Profiles: At the Intersection of Biology and Chemistry

A person works in the Biochemistry lab

By Vivian Mason


The Department of Biochemistry and Molecular Biology is an integral part of the F. Edward Hébert School of Medicine at the Uniformed Services University of the Health Sciences (USU). This dynamic department examines how biological molecules interact to drive the highly complex cellular processes of diverse living organisms. Eleven faculty members are actively engaged in teaching and conducting research in areas that include a broad spectrum of modern biochemistry, structural biology, biophysics, cell biology, cancer, neuroscience, proteomics, genetics and genomics, among others. 

The multidisciplinary nature of both biochemistry and molecular biology creates excitement in exploring the following areas: gene regulation, sphingolipid metabolism, human multidrug transporters, unusual metalloenzymes in anaerobic metabolism, RNA splicing, mitochondrial quality control, secretory pathway protein quality control and protein trafficking, among others. Thus, studying medicine, health, and disease from a molecular perspective can lead to fascinating insights and discoveries.

Three department faculty members―Yuanyi Feng, M.D., Ph.D.; Jeremy Rotty, Ph.D.; and Prasanna Satpute-Krishnan, Ph.D.―offer stimulating research specialization areas that awaken student imagination, assist in developing pioneering work, provide valued leadership/ training/mentorship to next-generation professionals, and encourage university collaborations. 


Yuanyi Feng, M.D., Ph.D., 

is associate professor of Biochemistry, as well as a developmental cell biologist whose research focuses on cerebral cortical neurogenesis, genome stability and cell differentiation, and neuroprogenitor vascular interaction. Although the recipient of a Ph.D. in molecular biophysics, her diverse background includes combining an interest in biochemistry and molecular biology with clinical medicine. Dr. Feng has also worked in a genetics lab where she studied genetic mutations that caused congenital brain disorders. 

“I enjoy learning and solving questions and medical-related mysteries. Research is never boring,” she says. “You always have new questions that come up. You always have something interesting to follow, and I really enjoy that. Research is very difficult. There’s a lot of frustration. But, it’s exciting and satisfying, too.” 

A portrait photo of Dr. Feng
Yuanyi Feng, M.D., Ph.D. [Image credit: Courtesy of USU]

As a scientist, she’s also interested in medical school education. Dr. Feng not only loves the idea of educating future doctors, but also teaching and combining it with research. She wants to bring new knowledge and concepts through her teaching. “I try to incorporate,” she adds, “a little insight from my research so that students are aware of the future of medicine. Through my work, I realize how my genetic background can contribute to helping with disease and treatment.”

However, her primary area of study is genetic mutations and the cerebral cortex, and how neurons are correctly made. If neurons aren’t made correctly, they can lead to neuropsychiatric and/or neurodegenerative disease risks, such as schizophrenia, obsessive compulsive disorder, ADHD (attention deficit hyperactivity disorder), and autism. 

Dr. Feng wants to include molecular techniques along with studying human diseases because it affects life quality and productivity. She notes, “Studying the genetic basis of diseases is quite satisfying. It’s important because it helps to better identify the pathogenesis to develop more effective treatments.”


Jeremy Rotty, Ph.D., 

is assistant professor of Biochemistry and a cell biologist. His research interests include cell migration and immunology. He studies the cytoskeleton to gain insight into immune cell migration. Dr. Rotty received an R01 award from the National Institutes of Health/National Institute of General Medical Sciences for “Extracellular Matrix Sensing in Cellular Signaling, Migration, and Wound Repair.”

“Throughout my career,” he explains, “I’ve always been interested in how cells move, their environment, and how they respond to whatever cues they’re receiving. I was really fascinated by cell migration and how aspects of the cell drive these behaviors. Eventually, I started thinking about immune cells and immunology, specifically macrophages and how they change their activities in response to what they find wherever they’re recruited.”

A portrait photo of Dr. Roddy
Jeremy Rotty, Ph.D. [Image credit: Courtesy of USU]

What really captured his interest was how macrophages respond to their microenvironment. So, Dr. Rotty decided to build his research along the lines of what he was not only interested in, but also on human elements that may potentially have an impact on disease and physiological processes. His recently-formed lab is essentially a cell biology lab that explores the processes in living cells. Running a lab is challenging, but he still tries to have a broad view. He adds, “You can’t be too rigid in your focus. You have to go where the science leads you and that can look different five years down the line.

“I’m becoming more interested in immune cells. The cytoskeleton and wound healing feature very substantially in what I’m working on now. While my focus narrows, I still retain a lot of the things I’ve acquired along the way. I’m learning that nothing’s wasted as I’ve moved beyond what I’ve learned,” Rotty said.

Dr. Rotty thinks that with increased collaboration comes the ability to ask bigger questions and to have more perspective on certain questions. He hopes that his program will help to establish more interactions and more collaborations. 

Even though research has always been his career focus, Dr. Rotty has always wanted to teach. He maintains, “It’s really been a wonderful experience teaching both graduate and medical students. They’re very inquisitive, open-minded, and want to know the principles behind things. Honestly, the topics that I lecture on right now don’t necessarily have, at first glance, fundamental impact on what my research is. Yet, I’ve started to think about my research in light of what I lecture about, and there’s been some cross-pollination that’s been really interesting concerning the role of metabolism. I don’t think I would have been thinking about it in that way necessarily had I not been lecturing along similar lines to the students.”

 

Prasanna Satpute-Krishnan, Ph.D., 

is assistant professor of Biochemistry and a cell biologist whose research interests include protein misfolding, trafficking, and quality control. She received an R01 award from NIH/NIGMS for “The Mechanistic Basis of Selective ER-Export of Misfolded Secretory Pathway Proteins.” 

As a cell biologist, she is intrigued by the problem of protein misfolding. Cells synthesize polypeptide chains or proteins that get folded into shapes that allow them to fit together to function as molecular machines that drive life processes. When proteins misfold into the wrong shape, they can jam up those life processes and lead to various diseases. Dr. Krishnan studies how cells recognize and destroy misfolded proteins in the secretory pathway. 

A portrait photo of Dr. Krishnan
Prasanna Satpute-Krishnan, Ph.D. [Image credit: Courtesy of USU]

“When cells fail to clear misfolded proteins, those proteins can accumulate. Accumulation of misfolded proteins is associated with fatal, degenerative diseases (e.g., Alzheimer’s, Parkinson’s, Huntington’s, amyotrophic lateral sclerosis, etc.) and the prion diseases (or progressive neurodegenerative disorders; e.g., mad cow disease, Creutzfeldt-Jakob disease, fatal familial insomnia, etc.),” she said.  Protein misfolding diseases are becoming increasingly prevalent in the aging population and, unfortunately, there are as yet no known cures. Of additional interest is the fact that traumatic brain injury has been associated with the accumulation of misfolded proteins in the brain tissue. 

Dr. Krishnan first became interested in the problem of misfolded proteins while working on her Ph.D. at Brown University in the lab of Dr. Tricia Serio. There, she demonstrated that the infectious prion protein can post-translationally remodel a mature, properly folded protein into the infectious prion form upon contact. The prion’s ability to transform others from good to dangerous reminded her of vampires and werewolves, and set her imagination afire. Adding to her intrigue, she also discovered that the chaperone HSP104―whose job it is to help refold the dangerous, infectious prion form into the native form―acted as a double agent because it also played a critical role in creating new prion seeds. 

These discoveries made her intensely curious about how cells identify and clear misfolded proteins. So, she started a project to investigate this fundamental cell biological problem as a postdoctoral fellow in the lab of Dr. Jennifer Lippincott-Schwartz at NIH, wherein “I discovered a surprising pathway cells use to obliterate misfolded secretory pathway proteins. I named this pathway RESET, and I continue to work on different aspects of RESET here at USU,” Krishnan said.

For Dr. Krishnan, the most exciting aspect of her lab’s research process is “watching cell biological processes transpire right before my eyes” by using live cell imaging methods. “We tag proteins with fluorescent markers that are readily detectable by confocal microscopy to watch the proteins engage in dynamic processes. By combining live cell imaging with biochemical methods, we are making very detailed and mechanistic discoveries about how cells manage misfolded proteins,” she said.

“Advances in combating protein misfolding diseases, including Alzheimer’s, have been few and far between. The major hurdle in making progress has been our lack of understanding of the fundamental mechanisms that underlie these diseases. Without this understanding, our only option has been to shoot in the dark in hopes of blindly hitting upon the right target for therapeutic intervention. As a group leader, I’m investing in the future generation of scientists to perform basic cell biological research to dissect the mechanistic basis of protein misfolding diseases so that we can tackle them through directed approaches.”