Gabriel Loeb, MD, PhD

2025 Carl W. Gottschalk Research Scholar Grant

Institution: UCSF

Project Title: Discovery of Novel Kidney Disease Genes from Polygenic Loci Using Functional Genomics

How would you sum up your overall research focus in one sentence?

Our lab uses human genetics and advanced experimental models to understand mechanisms underlying chronic kidney disease.

Provide a brief overview of the research you will conduct with help from the grant.

Genetics plays an enormous role in our risk of kidney disease. For ~90% of people with chronic kidney disease this risk is polygenic—driven by many regions of the genome, rather than mutation in a single gene. Our lab's overarching hypothesis is that understanding the molecular mechanisms underlying these genetic risk factors will provide critical insights into the biology of kidney disease and enable the development of more effective therapies for people living with kidney disease. We will use this funding to discover new genes that mediate the genetic risk of kidney disease using a combination of functional genomics, machine learning, and advanced experimental models.

What inspired you to focus your research in this area?

I am inspired by my patients. As a nephrology fellow I found it stunning that there were so many genetic kidney diseases for which the genes were known but for which we lacked treatments. I now have a kidney disease clinic dedicated to the care of people with genetic and familial kidney disease. I wanted and continue to want to be able to help prevent kidney disease for these patients.

I am also inspired by the challenge of understanding the mechanisms underlying human disease. Human genetics is one of the best tools to understand how breaking a particular gene, pathway, or cell type can cause disease in humans. Genetics can therefore help us discover which genes, pathways, and cell types we need to fix to treat and cure disease. I want to use genetics to discover the biology underlying human kidney disease.

What impact do you hope your research will have on patients?

My laboratory's goal is to do the basic research that enables the next generation of kidney therapies. Our goal is simple—doing the fundamental research that makes it possible to prevent kidney failure.

What has surprised you most about your career?

There has already been so much serendipity in my career. I have been interested in a career in science since a young age—although I originally imagined being a marine biologist working on the biggest marine mammals, not a molecular biologist working on how microscopic genes cause human disease. I didn't envision going to medical school until after college, when I met a physician-scientist in a nearby laboratory and he let me experience what a unique opportunity it was to be able to take care of patients and try to understand their diseases at a molecular level. I didn't envision becoming a nephrologist until late in my internal medicine residency when I realized both how much I loved taking care of patients with kidney and electrolyte problems and how much unmet need there is in our field. And the lab work I am pursuing now crystallized when I was working with my postdoctoral mentor—Dr. Jeremy Reiter—if I hadn't chosen him as my mentor I would be working on a completely different set of problems today.

What advice would you give to others to encourage them to apply for this grant funding?

Dare to be different—in the field, questions, and approaches you pursue.

Something you may not know about me is…

I grew up in Tucson, Arizona and competing in my high school science fair was a formative experience. Working with a biomedical engineer at the University of Arizona I took images of fruit with a novel imaging technique called Optical Coherence Tomography (which now is used clinically in the evaluation of people with eye diseases). I still can't believe that Dr. Barton let a high school student spend so much time in her laboratory. That experience was my first taste of serious science and my first experience of being able to see something no other human had seen by using a novel technology.

In my free time, I like to…

Run and cycle on dirt trails.