Advice from an alumna: ‘Do as your mother tells you’

Grace Milauskas
May 03, 2022

Sometimes life's journey is not a direct route but one with bends and ups and downs. Alumna Cynthia L. Bristow, Ph.D., has had her fair share of twists and turns.

Cynthia L. Bristow, Ph.D
Cynthia L. Bristow, Ph.D.

Her career after college started at a construction company in Orlando, Florida, that was building a large concrete tank in a treatment plant. She learned to use power tools, tie rebar, finish concrete and literally shovel a particular substance found in treatment plants. Then, armed with a math degree and construction experience, Dr. Bristow relocated to Charleston, where she was hired as a secretary in the registrar's office at MUSC

While working in the registrar's office, she learned about the biometry department and eventually earned a Master of Science under the biometry chair, Dr. M.C. Miller, III. There Bristow became involved in a project to model the immune system. Due to her mother's insistence, who was the executive assistant of the S.C. Commission on Higher Education, Bristow met with Dr. George P. Fulton, the associate director for Health Sciences and retired Boston University biology professor, for lunch. They began to discuss the immune system project she was working on during their time together, which led to many questions about how the immune system might discriminate between toxins, nutrients and inert material.

Little did Bristow know that Fulton had written to pioneer immunologist Dr. H. Hugh Fudenberg, chair of the MUSC Department of Basic and Clinical Immunology and Microbiology, to indicate that she was interested in the Ph.D. program and would be making an appointment to discuss her application.

"Southern manners clearly obligated me to follow through, even though I had no intention of applying. However, with Fudenberg's urging, I applied and was later awarded a Ph.D. under the direction of Dr. Robert J. Boackle. So, to all who read this, do as your mother tells you," said Bristow.

When her time at MUSC ended, Bristow served as an assistant professor at UNC-Chapel Hill for several years and completed a clinical fellowship in medical laboratory immunology (CPEP) under the guidance of Dr. James D. Folds.

After studying dendritic cells at The Rockefeller University in the laboratory of Dr. Ralph Steinman, Bristow accepted a position as an assistant professor of medicine at the Icahn School of Medicine at Mount Sinai University. Before stepping down from academic research, she was also an assistant professor of medicine at Weill Cornell Medical College. She then moved her laboratory to the Long Island High Technology Incubator at Stony Brook University with the goal of developing orally available small molecules that target the ability of immune cells to discriminate foreign material (antigens), nutrients (lipoproteins) and inert material (self).

With funding from the Institute for Human Genetics and Biochemistry, the lead small-molecule, Alphataxin, has been tested in a mouse model of kidney cancer and shown to increase the number of tumor-infiltrating CD4+ T cells. In addition, working independently and in combination with immune checkpoint inhibitors, it decreases tumor growth and metastasis dramatically.

Bristow's biotechnology company, Alpha-1 Biologics, was founded in June 2011. The company is currently conducting a study to determine the efficacy of Alphataxin in a mouse model of colon cancer and further characterize the functions and phenotypes of tumor-infiltrating immune cells.

"With a little bit of luck and with the opening of unexpected opportunities, I answered the question about the specificity of the immune system that I first posed to Dr. Fulton over lunch – a lunch that I had hesitantly attended only out of respect for my mother's wishes," said Bristow.

We asked Dr. Bristow to share some of her thoughts about science and her MUSC experiences.

What drives your commitment to science?

One of my good friends once told me that numbers are my toys. This was, of course, the underlying reason for my interest in math and biostatistics. Funnily, I made As and Bs in math and statistics classes. Still, I made the highest grade in my biology class at Winthrop University, not understanding at the time that my real interest was biology. However, once I became interested in how the immune system works, it became a quest from which I could not turn away. If you’ve ever played softball, when a hit ball is in the air, and you have your glove up and are running with the ball locked in your sights, you just can’t be called off.

How has your experience at MUSC and the College of Graduate Studies impacted your approach to science and opportunities for the future?

Let me preface this answer by explaining my most impactful discovery, a biochemical pathway that induces lymphocyte locomotion and involves an enzyme that acts as a cellular receptor, not as an enzyme. The binding of an enzyme inhibitor to the cell surface initiates the pathway. This protein complex subsequently links up with members of the family of low-density lipoprotein (LDL) receptors which induce cellular internalization of the entire receptor aggregate and associated cargo, including viruses, LDL and recycling receptors that return to the cell surface during a process of cellular locomotion. Discovering this pathway required me to understand enzyme kinetics, cellular activities and signaling. Finally, to develop an orally available small molecule to act as a surrogate for the enzyme inhibitor, I needed to have a broad knowledge of biochemistry and cellular immunology.

The craziest part of this story is that I was admitted into the Ph.D. program in immunology and microbiology despite never having taken a chemistry class – then or now. Of course, I would not recommend to the faint of heart that they try doing things this way, and I faced an unexpected amount of backlash because, unknowingly to me, my lack of chemistry was a contentious matter within the department. However, those professors who supported me as a student have given me lifelong support, and they know I hold them dear for teaching me how to succeed as a scientist and a colleague.

What advice would you give to current students?

I have two thoughts I would share, both from my father. I said to him once, “I have been really lucky in my career,” to which he responded, “You have never been lucky. You have terrible luck. You just never give up!” The most important advice he gave me was about how to avoid getting defensive when being condescended to by those whose status is above mine but whose knowledge is below mine. He said simply, “That’s when you lead and teach.”

Going forward, what things do you think MUSC and CGS should be focusing on for the future?

Careers. Jobs. Social media. Options after graduation should be transparent to CGS students from the beginning, including the likelihood of success within those options. This is especially important for women because we are still living with ingrained sexism in life sciences. Both women and men in life sciences need to be educated about how to appropriately make eye contact, appropriately interview in a pregnancy situation, appropriately lead without condescension and how to comprehend where we line up within our network in 3D - when to follow and when not to follow, and when to lead.