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.

With her bladder now under control, Gayle Osborne can pursue her passion for travel without trepidation

Gayle Osborne gets up close with an African lion while on safari in Zimbabwe.

It was supposed to be a once in a lifetime opportunity for Gayle Osborne — walking with the lions as part of an African safari.  But that morning, when a van pulled up instead of a bus with a bathroom, she broke into a cold sweat.  What would she do if she needed to “go?”

A story that began as a “death sentence,” has now transformed into a tale of hope for Osborne after her visit with Daniel Hoffman, MD, assistant professor in the USF Health Urology.

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Twenty years after Osborne’s initial diagnosis of interstitial cystitis—an incurable condition managed only by treatment—she is looking forward to living a full life again.

Initially, Osborne’s recurring urinary tract infections (UTI), known as interstitial cystitis, landed her in a Charlotte, N.C. doctor’s office. When doctors in North Carolina led her to believe her cause was hopeless, she walked out of the doctor’s office in tears, uncertain of her next move.

A frequent traveler and an avid tennis league player, Osborne was determined the diagnosis would not take control of her life. She and her husband of 51 years, Alan, were born just 10 days apart and they both have the travel bug.

However, too many times she was met by her own body’s hardship.  “When we went on trips and I knew that there wasn’t a bathroom, I felt anxious because I just didn’t know how I was going to feel,” the 73-year-old Osborne said.  “If you’ve ever had a UTI — it’s that constant burning sensation.  I wouldn’t wish it on anyone.”

//www.youtube.com/watch?v=9eHVDGowWjA

After that visit in North Carolina, Osborne worked earnestly to find treatment by researching every resource she could get her hands on: newsletters, websites, advice from friends and family and other specialists.  Sadly, she always found herself at a dead end.

“I suffered, mostly in silence, because very few others could relate to my symptoms,” Osborne said.

Then, she heard about Dr. Hoffman’s expertise and emailed him. He emailed right back and she set up an appointment. During the initial visit, Dr. Hoffman told Osborne he would treat the symptoms and work to figure out how to give her relief. Listening and solving Osborne’s problem was his top priority.

“Gayle’s quality of life was crushed by her condition,” Dr. Hoffman said. “I could immediately tell that she had lost hope in finding improvement. We identified the symptoms that were truly bothering her and targeted these issues specifically, putting her back in control of her bladder.”

Osborne with USF Health urologist Dr. Daniel Hoffman | Photo by Michelle Young, USF Health Communications and Marketing

“His approach, demeanor, and treatment plan gave me immense hope. Dr. Hoffman was a godsend.  Somebody was finally listening,’” Osborne said.

Indeed, Dr. Hoffman’s approach differed from the doctors from whom she’d sought treatment from in the past.  Thanks to his compassionate assessment of directly treating the symptoms, Osborne perked up instantly.

“It’s just like when you go to a doctor and you say, ‘Hey I have a cold.’ The doctor won’t treat it with an antibiotic because it’s a virus. You tell the doctor you have a cough.  And he says ‘We’ll give you something for your cough.’ It’s the same thing with what I have, and that’s how Dr. Hoffman approached it,” Osborne added.

Osborne hiking in Knysna, South Africa

For Osborne, compassion is one of the most important traits of a top-notch physician. With tears in her eyes, she told Dr. Hoffman during that first visit, “Not one urologist I visited before you has approached this ‘death sentence’ with the knowledge, energy and hope you have given to me in the last hour. It has taken a huge burden off of my shoulders and given me a feeling that now we are on the right track!”

With her primary issues now under control, she continues to work with Dr. Hoffman on the symptoms. With the travel bug biting again, she and her husband are planning a trip to South America this fall, where they will hike Machu Picchu Mountain. And this time if a van pulls up, Osborne will hop on with a smile.

Osborne with her husband and traveling companion Alan.

Story by Shelby Kaplan and doctor-patient video by Michelle Young, USF Health Communications and Marketing; “Walking with lions” video and photos courtesy of Gayle Osborne

Dr Kapil Patel was recruited from Stanford University known for its preeminent center

Pulmonologist Kapil Patel, MD, arrived at USF Health full-time Sept. 1 with one overarching goal in mind: to help lead and strengthen the Lung Transplant Program at Tampa General Hospital while strategically working to create a Center of Excellence for Advanced Lung Disease.

He came from Stanford University Medical Center, home to one the few such specialty pulmonology centers in the United States, which is known for its exceptional patient outcomes and consistently ranked by U.S. News & World Report as one of the best in the nation.

Pulmonologist Dr. Kapil Patel was recruited to the USF Health Morsani College of Medicine from Stanford University Medical Center.

“Dr. Patel’s recruitment is significant for USF Internal Medicine, the patients of USF Health and Tampa General Hospital and the community at large. His move from Stanford University to head the lung transplantation program is a landmark, making this the first solid organ transplant program to be part of USF in 35 years,” said John Sinnott, MD, chair of the Department of Internal Medicine, USF Health Morsani College of Medicine. “Dr. Patel’s vision for a center for advanced lung disease will place USF and Tampa General at the forefront of caring for patients with lung diseases in the United States.”

A center like the one at Stanford promotes continuity of care, allowing patients to be conveniently treated in one place by physicians who subspecialize in complex lung disorders, while cohesively providing the latest advances in medical and surgical care, said Dr. Patel, assistant professor of medicine in the Morsani College of Medicine’s Division of Pulmonary, Critical Care and Sleep Medicine and medical director for lung transplant, interstitial lung disease and adult cystic fibrosis.

“As you bring academic research to the forefront, it also opens opportunities for patients to participate in clinical trials that can afford alternatives to treatment they may not otherwise receive elsewhere,” he said.

Dr. Patel most recently directed the Stanford’s Interstitial Lung Disease (ILD) Program, one of the arms of the medical school’s Center for Advanced Lung Disease. He helped build physician referrals to Stanford’s ILD program from 100 to more than 200 in just over two years.

Providing integrated subspecialty care for complex lung diseases

Dr. Patel says he was attracted to USF Health by the opportunity to serve as medical director of an academic-affiliated lung transplant program and to build upon the solid foundation laid by Tampa General’s transplant team to create what could be Florida’s first center for advanced lung disease.

He plans to work with colleagues in USF Health Internal Medicine and Tampa General over the next several years to develop a center of excellence serving as the umbrella for four interconnected programs:

• Lung Transplantation: Tampa General already has an active program accredited by the United Network of Organ Sharing – one of five in Florida – and has performed more than 480 total adult lung transplants (single and double) since 2002. The program’s one-year patient survival rate of more than 91 percent and three-year survival rate of more than 71 percent both exceed national survival rate statistics. Dr. Patel plans to selectively grow a larger program.

“Selective is the way to go to do the right thing for patients. It is critical to identify appropriate candidates in need of transplant and to understand the limitations to transplant, so you do not push the limits too far,” he said. “We want to be confident that the surgery will go well, so the patient leaves the hospital with a new life.”

Since arriving here, Dr. Patel has worked closely with USF Health-affiliated cardiothoracic surgeon Christiano Caldeira, MD, of Florida Advanced Cardiothoracic Surgery, who serves as surgical director of the heart and lung transplant programs at TGH. They take donor calls together, jointly decide which donor organs are the healthiest for recipients, and co-manage lung transplant patients in the intensive care unit (ICU).

Dr. Patel with Nicole Davis, RN, a lung transplant coordinator at Tampa General Hospital.

• Interstitial Lung Disease, or ILD (also known as pulmonary fibrosis): This new program would manage the care of patients with a group of lung disorders causing tissue deep in the lungs to progressively stiffen and scar, which affects the ability to get enough oxygen into the bloodstream. Currently, Dr. Patel said, Florida has no ILD program certified by the Pulmonary Fibrosis Foundation (PFF) Care Center Network. Dr. Patel will lead an initiative by USF and TGH to establish the first.

• Cystic Fibrosis: Cystic fibrosis is an inherited disease that causes thick mucus to build up in the lungs, leading to repeated, serious lung infections. The Cystic Fibrosis Program at TGH is the largest adult program in the state certified and supported by the Cystic Fibrosis Foundation.

• Pulmonary Hypertension: USF Health pulmonologist Ricardo Restrepo-Jaramillo,MD, assistant professor of medicine, specializes in pulmonary hypertension – high blood pressure that occurs in the arteries that go from the heart to the lungs and may eventually lead to heart failure. He will become director of the new USF pulmonary hypertension program at TGH, Dr. Patel said.

Lung transplants are typically performed for people likely to die from lung disease within one to two years, when other treatments like medications or breathing devices no longer work, according to the National Heart, Lung and Blood Institute. ILD and cystic fibrosis are both conditions accounting for the most lung transplants nationwide, Dr. Patel said, with pulmonary hypertension affecting a smaller population of patients needing transplants.

Collaborating with community physicians

To create an integrated center, Dr. Patel plans to bring several pulmonologists with research as well as clinical expertise into the lung transplant program he directs, as well as recruit subspecialty directors for the ILD and cystic fibrosis programs. He will also add nurse practitioners to a team already supported by TGH nurse coordinators, respiratory therapists, social workers, dietitians and a pharmacist.

“When you manage patients with advanced lung disease, it takes a multidisciplinary team of professionals skilled in pre and post-transplant,” he said. “These are patients with complex conditions who need a lot of support and coordination,”

Dr. Patel sees patients at the Cardiac and Lung Transplant Clinic based at Harbourside Medical Tower.

More immediately, though, he is focusing on selectively increasing the referral base of patients by meeting with community physicians across the Tampa Bay region and seeing established pre-transplant patients in the clinic at Harbourside Medical Tower, Tampa General campus.

“I want doctors in the community to know that we are here to collaborate in the care of patients with advanced lung diseases,” Dr. Patel said. “Our availability is a priority, and ensuring the shortening of turn-around times for initial clinic visits is crucial, so that patients referred to the USF-TGH program are evaluated for medical care or transplant within weeks, not months. When someone needs a transplant, they need to be seen yesterday, and we work to intervene early.”

Advances in pulmonary transplant treatment

Over the last decade, advances in surgical techniques and significant improvements in post-operative care have contributed to improved survival of pulmonary transplant patients.

“We’ve gotten better at understanding what it takes to get these patients through transplants with fewer complications,” Dr. Patel said. “Once you get patients through the ICU following transplant, their chances of recovery and surviving a year or more out are much better.”

Medical therapy has also improved. For example, in 2014 the FDA approved the first medications (pirfenidone and nintedanib) to treat the most common type of pulmonary fibrosis, known as idiopathic pulmonary fibrosis (IPF). Until then, lung transplant was the only option for these patients, said Dr. Patel, who at Stanford led several site clinical trials testing the effectiveness of drugs for IPF.

Dr. Patel received his MD degree from the Medical University of Lublin in Poland. He completed a fellowship in pulmonary and critical care medicine at the University of Vermont and a dual heart-lung and lung fellowship at Stanford University Medical Center. He worked in private practice in Baltimore as well as holding faculty positions at the University of Vermont College of Medicine, the University of Maryland Medical Center, and Stanford.

Dr. Patel is a member of the American College of Chest Physicians and the International Society for Heart and Lung Transplantation.

A USF-TGH Center for Advanced Lung Disease won’t happen overnight. But Dr. Patel is confident that the vision can become a reality one purposeful step at a time.

“That’s why I came here,” he said. “We have a strong foundation and the pieces to grow.”

Photos by Eric Younghans, USF Health Communications and Marketing