From ‘army brat’ to ID chief, Rajat Madan, MD, PhD, takes on superbugs at U of A

For Rajat Madan, MD, PhD, the new Division of Infectious Diseases chief at the University of Arizona College of Medicine – Tucson’s Department of Medicine, the key to tackling antimicrobial resistance lies not only in the pathogen, but in how the human host responds.

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The physician-scientist, who starts in this post in January, comes from the University of Cincinnati where he was a professor of medicine on the infectious diseases faculty since 2014. He replaces Elizabeth Connick, MD, a renowned HIV researcher who retired as infectious diseases division chief a year ago, after having held the position since 2016.

Dr. Madan attacks antimicrobial resistance — which poses a global health threat from “superbugs” responsible for 1.27 million deaths worldwide and over 35,000 in the U.S. in 2019 — not directly, but employs an oblique maneuver, in military parlance, to hit the flank at an angle while holding the larger organism in check.

His approach, he says, doesn’t simply attack the organism itself, but seeks to better understand the genetics and molecular pathways behind the host response to infection and develop novel precision medicine-engineered therapeutic solutions to strengthen those, too.

All of this makes perfect sense when you consider how Dr. Madan grew up — a self-proclaimed “army brat” in India.

From army brat to VA physician

“My dad was a surgeon with the Indian Army, and I was born in this small town called Ambala in the military hospital there close to Punjab in North India,” Dr. Madan said. “I had lots of wonderful life experiences because my family moved every three years and we would go to different places all over India. At this time, my mom supported my sister and me, and took care of everything on the home front.”

He finished high school at Army School in Bareilly, Uttar Pradesh, and earned his medical degree at the JLN Medical College in Ajmer, Rajasthan, in 2000. Ajmer, he said, is a desert town much like Tucson, with desert landscapes surrounded by mountains. “That’s where I met my wife,” Dr. Madan said. “We went to medical school together.”

An endocrinologist, his wife, Ruchi Bhabhra, MD, PhD, works at a Cincinnati-based clinical research organization where she serves as medical director for clinical trials on rare endocrine disorders.

He did his doctoral studies at the University of Cincinnati, earning his PhD (2001-08) in molecular and developmental biology and immunology. He did his residency training at University of Cincinnati-affiliated The Christ Hospital (2008-11). And he did his fellowship training at the University of Virginia (2011-14), returning to Cincinnati afterward to join the faculty there. He also served as an attending physician at the Cincinnati VA Medical Center and will serve at the Tucson VA Medical Center as well.

Allies in battling superbugs

“I’m delighted to welcome Dr. Madan to the Department of Medicine,” said DOM Chair James K. Liao, MD, a professor in the Division of Cardiology and a renowned cardiovascular disease researcher. “Dr. Madan brings a wealth of experience in clinical leadership, education and research that will benefit our patients, faculty and trainees. I look forward to working with him to implement a vision for growth and preeminence of our Infectious Diseases Division.”

In addition to molecular pathways, Dr. Madan’s research focuses also on how host factors like the gut microbiome, immune system and metabolism (e.g., bile acids, obesity, etc.) impact infectious disease outcomes, particularly for pathogens like Clostridioides difficile, also known as C. diff, using advanced techniques like single-cell transcriptomics and metagenomics in preclinical models and patient studies to target a polymorphism in the gene for leptin receptor. C. diff infections contribute to about 71% of health care-associated gastrointestinal infections, resulting in severe diarrhea, colon inflammation and even death. His current studies seek to better define host genetic and immune mediators both beneficial and/or harmful after C. diff infections.

“In my research, looking at a particular host genetic polymorphism in the gene for leptin receptor, we found that having what we call the derived allele, or the mutant allele — not the ancestral allele — increased your risk of being diagnosed with C. diff infection threefold,” Dr. Madan said. “And the risk of having more severe outcomes after an infection was increased about sixfold with this group of individuals.”

By sequencing the RNA of neutrophils, cells that lead the attack against bacteria like C. diff, his research team has been able to identify subpopulations or different cellular states of these cells that tell them which state or phenotype may have enzymes and proteins that could be more damaging to the pathogen and/or the host — and which may be associated with worse patient outcomes. These key findings from the Madan Lab have been accepted for publication by the journal Infection and Immunity, and another set of findings are under review by the journal Gut Microbes. These results from the Madan Lab have the potential to shift the treatment paradigm of various pathogens including those with significant antimicrobial resistance.

Dr. Madan added, “We are already at a point in the field of infectious diseases where antimicrobial resistance is so high, we’re struggling to keep up with developing newer therapies that target the pathogen or bug. So, instead, we want to see if we can do host-targeted therapeutics” to find out why some people don’t get sick and others do, and how to tailor therapies to reduce incidence and improve patient outcomes.

Future research targets, he said, include highly resistant gram-negative bacteria like Pseudomonas, Stenotrophomonas and Enterobacter, for which there aren’t very good antibiotic preventatives.

A place to grow and foster growth

Dr. Madan said he learned about the infectious diseases division chief position from U of A College of Veterinary Medicine colleagues who work with him on C. diff research.

In addition to enthusiastic support from Dr. Liao, Dr. Madan said he was impressed by the atmosphere at the College of Medicine – Tucson, including the energy of senior faculty members such as Valley Fever Center for Excellence director John Galgiani, MD, and the dynamism of several younger faculty members in his division here.

“I realized this is a place where I can grow and gives me an opportunity to build a pipeline for the next generation of physicians and scientists in infectious diseases. In addition, I’m excited about the possibility of continuing to do groundbreaking research, where we can address current and emerging threats, and try to develop the next generation of therapeutics for treatment of infections,” Dr. Madan said.

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