Ishikawa and Mezzacappa Present the 15th Annual Dostanic Lecture

The 2026 Iva Dostanic, MD, PhD, Physician-Scientist Trainee Award of the Department of Internal Medicine was presented to two junior faculty: Genta Ishikawa, MD, MPH, of Pulmonary, Critical Care, and Sleep Medicine, and Catherine Mezzacappa, MD, MPH, PhD, of Digestive Diseases.

The recipients of the award presented their research findings during the 15th Annual Iva Dostanic Lecture that took place on Thursday, June 18, 2026 at a special medical grand rounds.

“Weekly grand rounds are a highlight of our academic week where we come together to learn and reflect," said Wolfram Goessling, MD, PhD, Ensign Professor of Medicine and Chair of Yale Department of Internal Medicine, while opening the lecture. “The Dostanic Lecture is a highlight amongst highlights where we both celebrate the legacy of our colleague, Iva, and the impact of our own faculty who we honor with this award every year.”

The lecture was created in memory of Iva Dostanic, MD, PhD, a former trainee of the ABIM Physician-Scientist Research Pathway in the Yale Traditional Internal Medicine Residency Training Program. Before she passed from ovarian cancer in 2011, the Department of Internal Medicine created an award and presented it to her. The award was later renamed in her memory.

In 2015, her parents—Dragana and Predrag Dostanic—pledged their estate to Yale School of Medicine (YSM) to endow the Iva Dostanic, MD, PhD, Physician-Scientist Fund to support physician-scientist career development.

Before handing the podium off to Peter Aronson, MD, Goessling acknowledged her parents, who sat in the audience, and expressed that what came to mind after meeting with them for the first time was love, commitment, and impact.

“It’s their love for their daughter that really led to us coming together here, and their commitment to celebrate her legacy and support our physician-scientists,” Goessling added.

Aronson spoke about Dostanic and gave the audience a glimpse into her life. He shared a detailed history about her passion for science and medicine, her research as a young scientist, and aspirations to become a physician-scientist.

He mentioned how Dostanic told her mother the happiest moment of her life was when she matched into the department’s internal medicine residency program. “I can attest that Iva matching here was a very happy event for us, too,” said Aronson, C. N. H. Long Professor of Medicine (Nephrology) and professor of cellular and molecular physiology, who was involved in her recruitment.

After he finished sharing Dostanic's history, he had a message for those who sat in the auditorium or tuned in on Zoom.

“For the students, residents, and trainees present in the audience today,” said Aronson, “our hope is that you will be inspired by Iva’s love for science and medicine, and especially by the enormous joy she found in her work right up until her last days. And we hope that inspired by Iva’s example, each of you will also find joy and fulfillment as you apply your own special gifts and talents to advance the science or practice or teaching of medicine.”

Erica Herzog, MD, PhD, John Slade Ely Professor of Medicine (Pulmonary) and professor of pathology, introduced her mentee, Ishikawa, and his path to becoming a physician-scientist.

Originally from Japan, Ishikawa worked as a pulmonologist in Tokyo, but decided to come to the United States to pursue a career as a physician-scientist in pursuit of researching potential therapies for the disease.

“Dr. Ishikawa was struck by the dearth of treatments for many respiratory diseases,” Herzog said. “He made the unusually committed decision to relocate his family to the United States because the U.S. has the best science in the world.”

Once in the U.S., he repeated his internal medicine training, and joined the Herzog lab in 2020 as a postdoctoral T32 research fellow with no basic science background. Herzog described how over the last six years, he has shown a relentless force of character, boundless optimism, extreme rigor, and utmost commitment and devotion to advancing respiratory medicine.

Ishikawa presented his research on a nerve-fibroblast axis in idiopathic pulmonary fibrosis.

“Idiopathic pulmonary fibrosis is a devastating lung disease characterized by progressive scarring of the lungs,” Ishikawa said. “The prognosis of IPF is comparable to that of many cancers, and although the disease course varies among patients, overall life expectancy without treatment is approximately three to five years after diagnosis.”

Since 2014, the U.S. Food and Drug Administration has approved three antifibrotic medications. Although the therapies slow down the progression of lung fibrosis, they do not reverse already established scarring. Currently, the only cure for the disease is lung transplantation, Ishikawa said.

Ishikawa described how lung fibrosis is initially triggered by repetitive alveolar injury to the epithelial cells. A healthy lung is capable of repairing this injury, but in IPF, an aberrant repair process occurs, accompanied by immune activation, profibrotic cytokine signaling, and the formation of scar tissue.

He said that much is unknown about the link between the nervous system and lung fibrosis. Ishikawa first began to research sympathetic nerves after Herzog surmised a connection to fibrosis. He sought to characterize the role of sympathetic innervation in the mammalian lung using both in vivo and in vitro models, as well as human lung samples.

His research first detected increased expression of alpha-1 adrenoreceptors—primary receptors for nerve-derived noradrenaline—in myofibroblasts, the key effector cells in pulmonary fibrosis, along with increased sympathetic innervation.

Ishikawa predicted that abrogating sympathetic innervation and signaling through this receptor would ameliorate lung fibrosis. His research led to the discovery that inhibiting the receptor—both in vivo and in vitro—mitigated pulmonary fibrosis.

The previously unrecognized nerve-fibroblast axis in pulmonary fibrosis raises important questions, said Ishikawa. He wonders what other factors contribute to maintaining this axis, including neurotrophins, neurotransmitters, and different types of nerves, such as sensory and parasympathetic nerves. Ishikawa looks forward to developing novel therapies to combat scar formation.

Mezzacappa was introduced by mentor Tamar Taddei, MD, professor of medicine (digestive diseases). Taddei outlined Mezzacappa’s journey to Yale, including how Mezzacappa has been with the department since training in the internal medicine residency program in 2018, and how she joined the section of Digestive Diseases as a T32 fellow in the investigative hepatology track.

“Dr. Mezzacappa is a hepatologist, epidemiologist, and emerging leader who brings rigor, creativity, joy, and deep compassion to everything she does,” said Taddei. “She has had tremendous achievements, while simultaneously enriching our section and our culture at Yale and the broader field of hepatology.”

Mezzacappa presented her research on gene-virus interactions in chronic liver disease, focusing on interactions between genetic risk for steatotic liver disease and human immunodeficiency virus (HIV) in the national VA system.

She provided background on how clinical management of liver disease, viral hepatitis, and cirrhosis have advanced over the past two decades. She noted how new antiviral therapies have changed the epidemiology of chronic liver disease.

“We are now living in a different era of chronic liver disease,” Mezzacappa said, “As people live longer with cirrhosis, we have more people living with cirrhosis attributable to steatotic liver disease, mostly from metabolic risk factors, but also from alcohol and its combination than from viral hepatitis in the VA population.”

In the general population, it’s estimated that around 35% of individuals have steatotic liver disease, Mezzacappa said. She noted how the disease tends to progress more rapidly in those with HIV due to several factors, including alterations of the immune environment within the liver, and how it’s been known for decades that there is a genetic predisposition to steatotic liver diseases.

She was interested in finding out if persons with HIV who are genetically predisposed to steatotic liver disease experience a greater risk of developing cirrhosis, whether there is an interaction, and whether clinicians need to screen and treat these individuals differently.

Mezzacappa investigated a sample of individuals with no history of viral hepatitis or primary liver disease who are at risk of cirrhosis. The findings of survival analyses show a clear dose response relationship of cirrhosis incidence over time with those who have one or more risk alleles.

The research demonstrated an interaction between HIV disease and a common variant in the glucokinase regulatory protein (GCKR) gene on the risk of cirrhosis. Individuals with both HIV and at least one copy of this variant were at significantly higher risk of developing cirrhosis after accounting for known risk factors for liver disease such as age, diabetes, and alcohol consumption.

“We have a lot of good clinical predictors for liver disease,” added Mezzacappa. “In order to use this testing, we need to know whether genetics can add clinical utility to identify risk and to target our treatments.”

Mezzacappa said the next steps are to assess for novel genetic variants associated with progression of liver disease—cirrhosis or hepatocellular carcinoma—in people with HIV and to further evaluate the role of viral load and antiretroviral therapies.

“We need to further investigate how these contribute and interact with genetic risk, and externally validate these results, especially in a cohort that includes more women.”

She suggests genetic testing could help determine which individuals should receive intensive therapies for steatotic liver disease. Starting with a different first line treatment for people with this genetic predisposition, especially those with an additional factor such as HIV, should be considered, she said.

“I think it's essential to not stop at identifying these associations, but thinking about how these can influence our medical decision making,” stated Mezzacappa.

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