Connecting Genetics, Discovery and Patient Care: Dr. Santhi Ganesh on the Future of Vascular Genetic Medicine

For Dr. Santhi Ganesh, some of the most important scientific questions begin with something that does not quite make sense.

As a cardiologist and physician-scientist, Dr. Ganesh has built her clinical and research career around understanding diseases that affect the structure and function of arteries. Her work focuses on vascular genetics and conditions including fibromuscular dysplasia (FMD), spontaneous coronary artery dissection (SCAD), pediatric renovascular hypertension, aneurysm and dissection syndromes, and other inherited or poorly understood arteriopathies.

What drew her to these conditions was the opportunity to work at the intersection of genetics, vascular biology, and clinical medicine.

“Many of the patients we see have significant vascular disease, but historically we have had limited ability to explain why it developed, predict who is at greatest risk, or offer treatments directed at the underlying biology,” she explains. “Genetics provides a way into those questions.”

That perspective has shaped the evolution of her lab, where genetic discoveries are increasingly being connected to the biological mechanisms that influence vascular cells and arterial structure. The ultimate goal is not simply to identify genes associated with disease, but to understand what those discoveries reveal about vascular biology and how that knowledge can be translated into better care.

From Discovery to Better Treatments

Dr. Ganesh’s research seeks to understand why some arteries become susceptible to abnormal remodeling, aneurysm, dissection, and other complications. Her team approaches these questions using human genetics and genomics alongside experimental biology and increasingly sophisticated technologies.

Researchers can now combine genomic data with a number of tools, including transcriptomics, proteomics, single-cell approaches, genome editing, and vascular model systems. These tools make it possible to move from identifying genetic factors associated with disease to investigating how those factors affect vascular cells and how arteries respond to mechanical stress.

For Dr. Ganesh, connecting those pieces is key.

“Finding a gene associated with disease is important, but it is really the beginning rather than the endpoint,” she says. “We want to understand what our new discoveries tell us about arterial biology, identify pathways that can be modified, and eventually develop treatments that prevent disease progression or vascular complications.”

Her work at the University of Michigan, along with the newly launched international Advancing Learning and Innovation in a Global Network for Fibromuscular Dysplasia (ALIGN-FMD) network and leadership of global efforts to understand SCAD in collaboration with the Canadian SCAD registry, is helping build the patient cohorts and collaborative infrastructure needed to advance research into rare vascular diseases and move toward a more precise approach to diagnosis and treatment.

A New Era for Rare Vascular Disease

Among the developments Dr. Ganesh finds most exciting is the growing ability to experimentally investigate human genetic discoveries.

Technologies such as genome sequencing, manipulation of gene expression, genome editing, single-cell genomics and engineered tissue models allow researchers to ask not only whether a genetic variant is associated with disease, but what that variant actually does in human vascular cells and how it affects vascular function.

“That convergence is changing what is possible in our research of rare and not-so-rare diseases,” she says.

For a cardiologist, the possibility of “interventional genetics”—using genetic discoveries to inform and perform interventions—is particularly exciting.

“I am eager to see the impact we can have on patients that have struggled with diseases that have gone without answers for too long”.

The path from discovery to treatment, however, requires collaboration, rigorous experimentation and well-developed patient cohorts. Rare diseases can be especially challenging because individual institutions may see relatively small numbers of patients.

That makes building connections across disciplines essential to Dr. Ganesh’s approach.

Building Communities Around Difficult Questions

One of the most rewarding aspects of Dr. Ganesh’s career has been watching questions that began with individual patients develop into much larger scientific programs.

Rare vascular diseases were historically understudied, she notes. Addressing that gap has required bringing together patients, clinicians, geneticists, vascular biologists, and other researchers to tackle questions that no single laboratory or institution could answer alone.

“I am fundamentally a collaborative person and a builder,” she says. “I enjoy taking an interesting problem, bringing together people with different expertise, and figuring out how to create something that did not previously exist.”

That might mean developing a scientific project, establishing a clinical program, creating a collaborative network or developing a new experimental approach.

Her work reflects that multidisciplinary philosophy. Through the Arterial Dysplasia Program, specialists including cardiologists, vascular surgeons, neurosurgeons, and neurologists, convene across total 13 different departments, units and sections across the medical campus, while her research collaborations extend to geneticists, engineers, biochemists, computational scientists and basic scientists.

She also directs M-BRISC, a program within the Center for cardiovascular disease in women and sex differences in cardiovascular diseases, where investigators are coming together across disciplines to examine disease mechanisms through the lens of sex differences as a biological signal. The work has created opportunities for collaboration across the University of Michigan campus and beyond.

“Many of the most interesting things we are doing now have come from bringing people together who would not have necessarily traditionally worked on the same question,” she says.

The Physician-Scientist and Mentor

Despite her growing research and leadership responsibilities, Dr. Ganesh remains grounded in clinical medicine.

“I was drawn to medicine because it combines science with a very immediate human purpose,” she says. “I am passionate about both clinical medicine and science, and my research efforts are really my way of extending my work to hopefully have a positive impact on as many patients as possible.”

Her path into research also revealed a passion for biology and genetics and their potential to transform medicine.

Mentorship is central to her work, and she has helped to develop the training and careers of numerous trainees who are now faculty and industry leaders across the U.S. She says it is deeply rewarding to help trainees and junior investigators develop their own scientific judgment and career paths.

In her role as Associate Chief of Cardiovascular Medicine, she hopes to continue strengthening the research community, developing the next generation of cardiovascular investigators, and creating connections between fundamental discovery and the clinical strengths of the division.

“I think science should be both rigorous and generous,” she says. “The best research environments are places where people exchange ideas freely, challenge one another thoughtfully, and help trainees and colleagues become better scientists.”

Staying Curious

Ultimately, Dr. Ganesh is inspired by difficult questions and unmet clinical needs—particularly in cardiovascular disease affecting women.

Patients with rare vascular diseases may arrive after years of uncertainty, sometimes having been told that little is known about why their disease occurred or what to expect next. For her, those unanswered questions are an invitation to investigate.

“I am motivated by the possibility that careful clinical observation, genetics, and experimental biology can turn an unexplained disease into a tractable scientific problem,” she says.

She does not have a single favorite quote that guides her, but she describes a principle that has shaped much of her career: stay curious about things that don’t quite make sense.

Some of the most interesting scientific questions begin with an observation that does not fit the prevailing explanation. Rather than dismissing those inconsistencies, Dr. Ganesh tries to pay attention to them—and to remain willing to change her mind when the evidence changes.

That curiosity continues to drive her work as a physician, scientist, mentor and collaborator.

And while much of her professional life is devoted to understanding genes, cells, arteries and disease, there is another role that matters deeply to her. Outside of work, she is a mom, and some of her favorite time is simply time spent with her daughter.

For Dr. Ganesh, the work of science may involve complex biology and unanswered questions, but its purpose remains straightforward: to turn discovery into meaningful advances for patients.