Dr. Jose Herazo-Maya’s research may help identify new treatments to improve survival in patients with idiopathic pulmonary fibrosis and severe COVID-19

Caring for patients struggling to breathe drives Dr. Jose Herazo-Maya’s research to find effective treatments for pulmonary fibrosis — an incurable, debilitating and often fatal disease that causes progressive lung scarring.

“The primary goal of our research team is to identify genes that predict survival (a low vs. high risk of dying) in patients with lung fibrosis,” said Herazo-Maya, MD, an associate professor and associate chief of pulmonary, critical care and sleep medicine at the USF Health Morsani College of Medicine. “We believe that if you target these genes, you can develop new treatments to help improve survival in these patients.”

The only two drugs currently approved to treat patients with idiopathic pulmonary fibrosis (pirfenidone and nintedanib) may help slow disease progression, but they do not stop lung scarring or prolong survival, and adverse effects can occur in up to half of people with IPF. Lung transplantation can improve survival, but organs are limited and not every patient with pulmonary disease is eligible for the complex surgery.

CT scans of (Above) normal lungs and (Below) lungs with  idiopathotic pulmonary fibrosis, characterized by scars and cysts. Images courtesy of Dr. Jose Herazo-Maya, USF Health

Pulmonary fibrosis is a disease in which the tissue in and between the air sacs of the lungs (alveoli) becomes damaged and scarred. As the tissue (interstitium) thickens and stiffens, it affects the ability to breathe and get enough oxygen into the bloodstream. While toxic environmental exposures, smoking and certain other diseases have been associated with pulmonary fibrosis, in most cases the cause is unknown (idiopathic). Median survival for patients diagnosed with idiopathic pulmonary fibrosis (IPF) is three to five years.

“IPF is a devasting disease that needs better therapeutic options to improve quality of life and save lives,” Dr. Herazo-Maya said. “For me, taking care of these patients is a constant reminder that we need to do better.”

A return to academic medicine

Dr. Herazo-Maya joined USF Health in January 2021 from NCH Healthcare System in Naples, Fla., where he spent nearly four years directing a growing Interstitial Lung Disease Program. Before that, the physician-scientist was an assistant professor at Yale University School of Medicine. He is an expert in genomics, with a focus on studying how gene expression influences immunity and its association with disease progression and outcomes.

USF Health physician scientist Jose Herazo-Maya, MD, (far right) in his USF Health Heart Institute laboratory with his research team. Photographed (l to r) are Carole Perrot, PhD; Bochra Tourki, PhD; Alyssa Arsenault, LPN; and Brenda Juan-Guardela, MD. — Photo by Allison Long, USF Health Communications and Marketing

At Yale Dr. Herazo-Maya was part of team that discovered a gene expression signature in blood that reliably forecasts the likelihood of mortality and poor outcomes from IPF. The team subsequently led an international study that validated this risk profile based on 52 genes. He was among the inventors on the patent for the IPF gene risk profile, since acquired by a global company seeking to develop the scientific breakthrough into a simple blood test to be used for patient care.

Dr. Herazo-Maya returned to academic medicine after several years of private practice in Naples, in part he says because he was frustrated by the lack of research progress to identify pulmonary fibrosis treatment options. A surge in patients battling severe lung scarring from COVID-19 complications also prompted his decision to recommit to translating discoveries from the laboratory back to the patient bedside.

Soon after arriving at the USF Health Heart Institute last year, Dr. Herazo-Maya quickly began building a pulmonary fibrosis research program with the generous support of a $1 million gift made by philanthropist Timothy Ubben to the USF Foundation. (In December 2021, Mr. Ubben gave an additional $5 million to create the Ubben Family Center for Pulmonary Fibrosis that will accelerate research leading to new tests and treatments for patients.)

Dr. Herazo-Maya, a member of the pulmonary and critical care team at Tampa General Hospital, also treats patients at the TGH Center for Advanced Lung Disease — including those being evaluated for lung transplant. Along with fellow USF Health pulmonologists Dr. Kapilkumar Patel and Dr. Debabrata Bandyopadhyay at this leading TGH Center, Dr. Herazo-Maya is an investigator for clinical trials testing potential new drugs to treat lung fibrosis.

Bochra Tourki, PhD, looks at a computer slide of immune cells from the lung tissue of a COVID-19 patient with pulmonary fibrosis. – Photo by Allison Long

The impact of witnessing “air hunger”

From the start of his medical career, Dr. Herazo-Maya was interested in both critical care and science. While conducting a postdoctoral fellowship at the University of Pittsburgh School of Medicine’s Simmons Center for Interstitial Lung Disease, he was invited by his faculty mentor and center director Nafali Kaminski, MD, to accompany a group of the center’s patients, physicians, and scientists on a boat trip along the city’s rivers.

“I remember the patients using oxygen had a very hard time getting into the boat. They could not even take a few steps without becoming short of breath,” Dr. Herazo-Maya said. “Seeing how those patients struggled to breathe – their feeling of air hunger – had a big impact on me wanting to take care of them.”

While certain patients with IPF can live well for years, others develop worsening disease and die quickly. No prognostic tool yet exists to tell doctors which patients will experience rapid progression of pulmonary fibrosis, and which will progress slowly. But Dr. Herazo-Maya and colleagues are working on a molecular-level test to do just that.

A tool to predict the clinical course of IPF or any other type of lung fibrosis could help patients and clinicians make better informed decisions about care, Dr. Herazo-Maya said. “For instance, if a rapid test indicated that a patient’s genetic predisposition to mortality was high, they might need to get to the hospital to receive more aggressive medical care, and possibly be evaluated for lung transplant while they are still relatively healthy enough to withstand transplant surgery.”

Dr. Herazo-Maya (far left) consults with (l to r) staff scientist Carole Perot, PhD; postdoctoral scholar Bochra Tourki, PhD; and clinical research coordinator Alyssa Arsenault, LPN. – Photo by Allison Long

Genomic risk prediction can also increase opportunities for drug discovery, he said. “Each one of the genes we analyze is a potential drug target. We can study them in the lab to understand how they work and possibly come up with novel therapies.”

Pivoting genomic research to COVID-19

As the COVID-19 pandemic unfolded in 2020, pulmonologists and other critical care clinicians were inundated by patients in respiratory distress.

As he helped treat the influx of hospitalized patients, Dr. Herazo-Maya noticed that, like IPF, severe COVID-19 could also damage the lung interstitium leading to severe scarring. He thought about finding more precise ways to distinguish between symptomatic individuals likely to recover at home with appropriate monitoring and those likely to end up in the intensive care unit (ICU) and die. A prognostic tool capable of detecting which patients were apt to do worse before they became seriously ill could help health care providers better allocate limited resources like ICU beds and ventilators, tailor interventions, and potentially save lives.

“At the time investigators were scrambling to identify gene profiles predictive of COVID-19 outcomes,” Dr. Herazo-Maya said. “So, our basic question was ‘Can we repurpose a gene risk profile known to predict mortality in IPF to predict mortality in those infected with a new coronavirus that can cause lung fibrosis as well?’”

The preliminary answer appears to be yes.

Dr. Herazo-Maya’s computer monitor displays heat maps depicting clusters of COVID-19 subjects identified as having a low vs. high risk of mortality (Below), based on a gene expression signature in blood. The recent research showed that a previously validated technique for predicting idiopathic lung fibrosis outcomes could be repurposed for COVID-19. – Photo by Allison Long | Heat map image courtesy of Dr. Herazo-Maya, USF Health

Earlier this year, a multicenter retrospective study led by USF Health’s Dr. Herazo-Maya demonstrated that a 50-gene signature associated with a high risk of dying from IPF can also predict poor outcomes (ICU admissions, mechanical ventilation, and death) in patients with COVID-19. The findings were reported in EBioMedicine, a publication of THE LANCET.

More studies are needed, but researchers and clinicians may soon be able to apply the gene risk profile to help advance the care of both COVID-19 and IPF patients, Dr. Herazo-Maya said. His laboratory is currently developing a blood test, based on a more selective group of the 50 genes, that can be easily applied in clinical practice.

Two distinct diseases, same gene risk profile

The overlapping gene expression profiles for COVID-19 and IPF look remarkably similar, Dr. Herazo-Maya said. “That suggests there are immune pathways shared between these two diseases.”

Using single-cell gene analyses, Dr. Herazo-Maya has identified specific immune cells – monocytes, neutrophils, and dendritic cells — as the primary source of gene expression changes in the high-risk COVID-19 gene profile. Interestingly, he said, monocytes can give rise to macrophages involved in triggering scar formation.

Brenda Perrot, PhD, works on an experiment.

Dr. Herazo-Maya received his MD degree from the University of Cartagena School of Medicine in Colombia. He completed a research fellowship in interstitial lung disease and residency training in internal medicine at the University of Pittsburgh School of Medicine. Specializing in pulmonary and critical care, he conducted postdoctoral training in genomics, computational biology, bioinformatics and molecular biology at Yale and Pittsburgh universities.

The Robert Wood Johnson Foundation and the Pulmonary Fibrosis Foundation funded his research in the past, and his current work is supported by the USF Foundation-Ubben Family Fund.

Dr. Herazo-Maya has published numerous peer-reviewed papers, including in such high-impact journals as the Nature Medicine, the Journal of Clinical Investigation, Lancet Respiratory Medicine, Science Translational Medicine and the American Journal of Respiratory and Critical Care Medicine. He is the coauthor of several book chapters on topics ranging from biomarkers in assessing and managing IPF to applying personalized medicine (‘omics) to lung fibrosis.

Dr. Herazo-Maya and his wife Dr. Brenda Juan-Guardela (right), assistant professor of medicine at USF Health and medical director of Respiratory Care Services at TGH, have collaborated on pulmonary fibrosis research throughout their medical careers. – Photo by Allison Long

Some things you may not know about Dr. Herazo-Maya

If he did not become a physician and researcher, Dr. Herazo-Maya says he would have been a marine biologist. Growing up near the beach in Cartagena, he snorkeled and was “fascinated by all the sea creatures.”

Dr. Herazo-Maya is married to pulmonologist Brenda Juan-Guardela, MD, an assistant professor of medicine at USF Health Morsani College of Medicine and medical director of Respiratory Care Services at TGH. They met in medical school, trained in the same laboratory as postdoctoral scholars, and continue to collaborate on pulmonary fibrosis research. They live in Tampa with their two sons Christian, 6, and Lucas, 4.

In his spare time, Dr. Herazo-Maya enjoys playing soccer and baseball with his sons in their yard and watching their youth soccer league games.