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.

USF Health’s Dr. Kami Kim probes the epigenetics of two global parasitic infections, malaria and toxoplasmosis

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While an undergraduate at Harvard University, Kami Kim, MD, participated in a research thesis project exploring leukemia’s resistance to chemotherapy and the effectiveness of combination drugs in combatting it.  While she was excited to help figure out (and publish) a mechanism, she recalls that she signed on for this laboratory research primarily “to help in get into medical school.”

Her interest in research intensified in medical school in early 1980s at the beginning of the domestic AIDS era, about the same time tuberculosis cases were exploding and malaria, once considered virtually eliminated as a major public health threat, began to re-emerge globally.

“It was clear that there was much to be done in infectious diseases research — a lot of interesting problems that needed to be solved,” said Dr. Kim, who joined the USF Health Morsani College of Medicine last year as a professor in the Department of Internal Medicine’s Division of Infectious Disease and International Medicine.

Kami Kim, MD, a USF Health professor of infectious disease, with her multidisciplinary laboratory research team, which includes expertise from the medicine, public health, mathematics and statistics

 Undergraduate laboratory work that sparked a lifelong passion for research

Basic science and clinical infectious diseases expertise

After clinical training as an infectious diseases fellow at the University of California San Francisco (UCSF) – and witnessing firsthand the devastating consequences of acquired immunodeficiency syndrome – Dr. Kim returned to laboratory research, with an emphasis on parasitic infectious diseases.  Meanwhile, she continued to see patients as an attending academic physician at some of the nation’s best hospitals in San Francisco and New York City.

That blend of rigorous clinical and basic science expertise makes Dr. Kim one of the first of several high-profile, energetic recruits who will help take USF Health’s global infectious disease research to the next level.

Dr. Kim came to USF Health in November 2017 from Albert Einstein College of Medicine in New York City, where she was a professor of medicine, microbiology and immunology, and pathology.  In addition to her laboratory research at USF, she consults monthly on infectious diseases cases at Tampa General Hospital. At Einstein, she directed the infectious diseases section of the Center for Epigenomics and helped launch and led the National Institutes of Health-funded Geographic Medicine and Emerging Infections Training Program, which supports interdisciplinary training in translational research for pre-doctoral students, post-doctoral research fellows and clinical fellows.

A plaque formation of the intracellular parasite Toxoplasma gondii

Seeking solutions to life-threatening global parasitic diseases

Dr. Kim’s USF Health research team, working out of a laboratory in the university’s research park, focuses on two major areas — malaria and toxoplasmosis.  The world’s most dangerous parasitic disease, malaria claims more than 2 million victims and 445,000 deaths yearly, primarily in sub-Saharan Africa. Toxoplasmosis, often asymptomatic, can be life-threatening to babies born to women infected during pregnancy and people with weakened immune systems.

• Toxoplasmosis project: Combining advanced techniques from genetics, cell biology and proteomics, the researchers investigate the ways that epigenetics – the interface of genetics and environmental factors – regulate development of chronic infection by the cat-borne gondii parasite. They seek to understand how this pervasive parasite switches back and forth between a rapidly dividing acute stage destructive to healthy tissue (tachyzoite) and a chronic, or dormant, stage, where bradyzoite forms within pseudocysts remain invisible to the immune system. Dr. Kim collaborates with other leading Toxoplasma experts: Distinguished USF Health Professor Michael White, PhD, a long-time colleague, as well as investigators at Indiana University, Pennsylvania State University and Albert Einstein College of Medicine.
• Malaria project: In the hot, wet regions of Africa, mosquitoes are ubiquitous and children exposed to malaria from birth may contract the infection several time a year. The overwhelming majority of clinical cases are uncomplicated, with flu-like symptoms of fever and malaise that typically resolve. Researchers are trying to determine why a small percentage of individuals, in particular certain children, are more likely to develop severe malaria with coma and death (cerebral malaria) or long-term neurological complications such as seizures and cognitive and behavioral problems. In particular, the USF team is assessing specific biomarkers, or genetic predispositions, and parasite or host factors that may help predict disease development or its outcomes.

 Dr. Kim discusses research correlating HIV co-infection with cerebral malaria.

Research instructor Iset Vera

Both research initiatives harness the latest genomic technology to better understand how immunity works within the framework of host-parasite interactions – all with the aim of devising better or first-time treatments.

Valuable insights into cerebral malaria, future therapies

With collaborators from the Blantyre Malaria Project, based in Malawi, Africa, Dr. Kim published a high-profile paper in mBIO in 2015 reporting for the first time that children co-infected with HIV were much more likely than those who were not to die from severe malaria. Autopsies of the children who died from cerebral malaria indicated that those with HIV had brain blood vessels more clogged with white blood cells and platelets than those of children with malaria alone.  HIV appeared to rev up brain inflammation that could lead to death.

In another study, published in Cell Host & Microbe in 2017, Dr. Kim and colleagues used neuroimaging, parasite transcript profiling and laboratory blood profiles to develop machine-learning models of malarial retinopathy and brain swelling. The researchers found that the interaction of high parasite biomass, low platelet levels and certain parasite protein variants that bind to the endothelial protein C receptor (EPCR) play a pivotal role in fatal cases of malaria. Their findings added strength to the rationale that anti-inflammatory and anticoagulant treatments counteracting the breakdown of endothelium may benefit those with severe malaria.

“We still don’t entirely know why some of these kids get super sick and have complications requiring hospitalization,” Dr. Kim said. “If we could figure that out we could save lives, reduce complications and use limited healthcare dollars more effectively in these under-resourced countries.”

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 The “Goldilocks” theory of immunity

When it comes to infectious diseases, too much of a good thing may make you sick.  Dr. Kim calls it the “Goldilocks” theory of immunity – not too much (overactive immune system) and not too little (under-responsive immune system).

For instance, “for someone with malaria the right amount of immunity might not be just the right amount if they already also have tuberculosis,” Dr. Kim said. “What we’re realizing now with the human immune response to parasites or other foreign invaders (pathogens) is that you have to get the balance just right, so you get rid of the pathogen without damaging the human host.”

Otherwise, she added, even after the pathogen is eliminated, long-term complications like a damaging autoimmune inflammatory condition may linger.

Rigorously studying the dynamics of host-parasite interaction – including how parasites hijack the epigenome, which adjusts specific genes in response to signals from the outside world such as diet and stress — is critical to bridging the gap between discovery and effective treatments for different subgroups of infected patients.

“Both the pathogen and the infected host are duking it out to see which one wins, so figuring out what’s happening on both sides is really important to understanding immunity – how our body fights off disease,” Dr. Kim said. “Using genomic information to tell us who’s most susceptible to certain conditions will likely help us to tailor therapies to the individual, or perhaps to know who needs to be vaccinated.”

Dr. Kim with Li-Min Ting, PhD, an assistant professor in the Department of Internal Medicine’s Division of Infectious Disease

 Striking the right balance of immunity

Potential applications for other diseases

Within their complex life cycles, both malaria and toxoplasma parasites have dormant forms that the human immune system can’t identify and kill, and antimicrobial drugs can’t touch.  For malaria, this silent form lurks in the liver. For Toxoplasma, cysts can settle quietly into the infected person’s brain and muscle tissue without replicating, sometimes for years, until weakened immunity reactivates the disease.

Dr. Kim and other researchers continue to look for new ways to combat chronic infection by parasites.

“Normally when treating a disease you think of killing the form that makes a person clinically symptomatic,” she said, “but with both malaria and Toxoplasma if you can kill the biologically silent form, which is absolutely essential for the disease to continue, you’re accomplishing the same thing.”

Although Dr. Kim’s group targets specific problems underlying malaria and toxoplasmosis, such immune research may have broad applications for understanding and treating other conditions.  For instance, atherosclerosis has been linked to the release of molecules from the immune system that can cause inflammation, blood vessel injury and plaque instability leading to heart attacks and stroke.

A T. gondii plaque assay

“Even though drug companies, because of financial return on investment, aren’t necessarily willing to invest in research on malaria host factors,” Dr. Kim said, “they are really interested in stroke and cardiovascular disease.  And the big players in the kind of inflammation seen in these two major diseases are platelets and monocytes” – the same inflammatory culprits implicated in cerebral malaria.

While more research is needed, perhaps statin and antiplatelet drugs already approved for another indication could be effective in helping combat malaria,” she said. “It’s entirely possible by better understanding what’s a good immune response to malaria in one situation and bad in another will lead to insights that can be used to develop treatments for other diseases, or insight into what’s protective in another disease.”

Pursuing new approaches to outsmart elusive pathogens

Dr. Kim received her MD degree from the Columbia College of Physicians and Surgeons in New York City. She completed her residency in medicine at Columbia-Presbyterian Medical Center, a clinical fellowship in infectious diseases at UC San Francisco, and two postdoctoral research fellowships – one in parasitology at San Francisco General Hospital and a second in microbiology and immunology at Stanford University.

Dr. Kim is a fellow of the Infectious Diseases Society of America and the American Academy of Microbiology. She is also an elected member of American Society for Clinical Investigation and the Association of American Physicians, national honor societies for physician-scientists. A recipient of the Burroughs Wellcome Fund (BWF) New Investigator Award in Molecular Parasitology early in her career, she has served on the BWF Postdoctoral Research Enrichment Program’s scientific advisory board since 2014.  She is a member of the NIH Pathogenic Eukaryotes Study Section.

The cutting-edge tools of computational genomics contribute to Dr. Kim’s work.

Throughout much of her career, Dr. Kim’s research has been funded by the National Institute of Allergy and Infectious Diseases.  She holds several patents, and was one of the first investigators to develop techniques to genetically manipulate T. gondii. She is the co-editor and currently preparing the third edition of Toxoplasma gondii, the Model Apicomplexan: Perspectives and Methods, a textbook widely considered the seminal source for scientists and physicians working with this parasite.

Dr. Kim said she was attracted to USF because of the university’s upward national trajectory and USF Health leadership’s commitment to building translational research and pursuing innovative approaches and excellence in all its academic missions. She is a member of the USF-wide Genomics Program.

“I enjoy being part of a USF clinical community that excels in the treatment of infectious diseases and working with physicians and scientists who do parasitology research,” she said.  “You constantly have to think outside the box and come up with clever strategies – because we’re dealing with pathogens that do not behave like they are supposed to.”

 Toxplasma parasite strategy for survival

Dr. Kim, one of the first investigators to develop techniques to genetically manipulate Toxoplasma gondii, co-edits a textbook widely considered the seminal source for scientists and physicians working with this parasite.

Some things you might not know about Dr. Kim

• Korean was her first language, and she also speaks Spanish.
• She enjoys food, arts and crafts, and travel. Countries she has visited include Korea, Malawi, South Africa, France, Japan, and Brazil.
• Kim is married to Thomas McDonald, MD, USF Health professor of cardiovascular sciences and director of the new Cardiogenetics Clinic. They have two sons who are both mathematicians, one in a mathematics PhD program and the other in college. They met in the cardiac intensive care unit at Columbia Presbyterian Medical Center when Dr. McDonald was a resident and Dr. Kim was rounding as a medical student.

Dr. Kim’s career as an infectious disease physician-scientist bridges basic research and clinical practice.

-Video and photos by Torie M. Doll, USF Health Communications and Marketing