Young scientists wishing to become independent investigators face a quandary: They each need to obtain an R01 research project grant, the Holy Grail of National Institutes of Health (NIH) grants. But qualifying for an R01 also requires funding—to develop a promising line of inquiry, produce results, and publish papers. How to overcome this catch-22?
Emily Happy Miller, M.D., Ph.D. ’14
Assistant professor of medicine and of microbiology & immunology
In March 2020, Dr. Miller was a second-year fellow in infectious diseases at Columbia University, pursuing research on viruses and planning to apply to the NIH for a K grant. Then came COVID-19.
In the time it takes to don an N95 face mask, Dr. Miller was reassigned to Columbia’s new COVID-19 inpatient service, postponing her career plans. “We were overwhelmed with seriously ill patients, and if you wanted to conduct research, it had to be clinically focused and related to COVID,” she recalls. The fledgling researcher wound up studying the neurological manifestations of infection with SARS-CoV-2, the virus that causes COVID-19, and how viral load affects the course of the disease.
“Obviously, it was a terrible time,” she adds. “Yet for me, it was also a formative experience. I had been studying these scary viruses in the lab for years, and now I was in the midst of an actual virus pandemic.”
As COVID-19 wound down, Dr. Miller realized that she wanted to continue with the kind of virology she’d been doing during her doctoral research at Einstein with her mentor, Kartik Chandran, Ph.D., professor of microbiology & immunology and a nationally renowned expert on emerging viruses. At that time, she had been focused on basic research—how the Ebola virus enters host cells—and now she wanted to add a clinical angle. The two scientists had kept in touch. And as soon as circumstances allowed, Dr. Chandran invited his protégé to rejoin his laboratory, this time as a faculty member and physician-scientist.
Upon her return to Einstein, Dr. Miller took aim at the betacoronavirus family, which includes SARS-CoV-2 as well as the viruses responsible for MERS (Middle East respiratory syndrome) and SARS (severe acute respiratory syndrome). After adding new publications to her curriculum vitae and receiving an internal career development award from the Einstein Montefiore Clinical and Translational Science Awards program, she obtained a highly competitive NIH K08 Mentored Clinical Scientist Research Career Development Award. With support from this grant, she is engineering vaccines and immunotherapies that offer broad protection against these fast-evolving pathogens.
No approved treatments are yet available for SARS or MERS, and antibody-based treatments for COVID-19 must regularly be tweaked to keep up with the latest SARS-CoV-2 variants. The problem with existing COVID-19 therapies is that they’re designed to target the S1 subunit of the virus’s spike protein, which initiates infection by docking the virus to host cells. Unfortunately, S1 regularly mutates, making the development of effective therapies a perpetual catch-up exercise.
Dr. Miller hopes to surmount this limitation by designing therapies targeting a different spike protein: the S2 subunit, by which SARS-CoV-2 fuses its membrane with the host-cell membrane in the second step of infection.
One good thing about the S2 subunit, she explains, is that it’s much less likely to mutate than S1. Another benefit: S2 is highly conserved among the many different betacoronaviruses. “That’s significant,” Dr. Miller says, “because it means an S2-based therapy that works for COVID could work for SARS and MERS, and perhaps for future betacoronavirus infections. One lesson I learned from Dr. Chandran and from COVID is that we need to prepare for the next pandemic, not just wait and respond to it.”
Dr. Miller says she’s been “incredibly fortunate” to have great mentors at Einstein. “I always tell graduate students that one of your most important decisions when picking a lab is not necessarily the subject area but the mentor—finding someone who can guide you through all the different steps toward becoming an investigator.”
Dr. Chandran says Dr. Miller is on a trajectory to become a leader in virus research. “Emily is combining her passion for virology with her clinical experience—including during the COVID-19 pandemic—to generate important new insights into countermeasures against several pandemic-risk viruses,” he says. Dr. Chandran is also the Gertrude and David Feinson Chair in Medicine, and the Harold and Muriel Block Faculty Scholar in Virology.
Kerry A. Morrone, M.D., M.S. ’07
Associate professor of pediatrics
The shortest distance between two points may be a straight line, but it’s not necessarily the best route. Witness Dr. Morrone’s 17-year journey from clinician to independently funded clinical researcher.
After graduating from Einstein, Dr. Morrone completed a residency and fellowship in pediatrics at Montefiore, eventually specializing in sickle-cell disease. “I was always interested in improving the care of kids with sickle-cell disease, but I never thought I’d apply for a formal research grant,” she says. “However, through my mentors and my evolution as a clinician, I came to understand what doing research requires and realized that I couldn’t just do it on the side.”
Dr. Morrone began climbing the clinical research ladder in 2019, winning an Empire Clinical Research Investigator Program training grant, a New York State initiative for training physicians in clinical research. Then came a K12 Clinical Scientist Institutional Career Development Program Award from the Agency for Healthcare Research and Quality (a component of the Department of Health and Human Services), supporting her master’s-level studies in Einstein’s Clinical Research Training Program (CRTP), where she learned about epidemiology, biostatistics, and data analysis.
Five years, two children, and one K08 grant later, Dr. Morrone was finally ready to launch her research career. “I think this long journey made it more fulfilling,” she says. “During my master’s, I realized exactly what I wanted to learn and investigate.”
Dr. Morrone’s K08 work builds on the results of her CRTP research project, which showed that people providing healthcare for young inpatients with sickle-cell disease often have trouble sticking to standard-of-care practices. Less-than-ideal care leaves these children susceptible to serious complications—notably acute chest syndrome (ACS), characterized by the sudden onset of chest pain, fever, and difficulty breathing. Unless properly treated, ACS can lead to irreversible lung damage and even death.
“We have ways to prevent ACS—using appropriate opioid dosing and incentive spirometers, for example—but this care is complicated,” says Dr. Morrone, now the director of the Pediatric Sickle-Cell Program at Children’s Hospital at Montefiore Einstein. “In my CRTP project I created a detailed care checklist, which helps but isn’t enough. There’s no one-size-fits-all approach to sickle-cell disease care. But given a patient’s condition, we can prioritize certain aspects of care.”
How to help caregivers prioritize those key aspects is the focus of Dr. Morrone’s new study. More specifically, she aims to identify barriers that prevent healthcare providers from delivering the best possible care to sickle-cell patients; develop an electronic health-record tool that supports clinical decision-making; and, finally, pilot-test that tool on an inpatient pediatric sickle-cell disease unit at Montefiore.
Since late 2023, the U.S. Food and Drug Administration has approved several gene therapies with potential for curing sickle-cell disease. “This remarkable clinical advance has given hope to many patients and their families,” says Dr. Morrone. “But for now, gene therapy for sickle-cell disease is appropriate for only some of our patients and carries many risks, including infection and infertility. In the meantime, we need to focus on improving standard sickle-cell disease care, so we can keep kids as healthy as possible until gene therapy becomes safer and more widely used.”
When she first started caring for patients with sickle-cell disease, Dr. Morrone says, “there was little enthusiasm in the pharmaceutical industry for improving sickle-cell disease care. There weren’t even any FDA-approved treatments for pediatric patients with sickle-cell disease. That has changed tremendously. It’s an exciting time, and I hope this recent progress spurs more young physicians and researchers into the field.”
Zheng Wang, Ph.D. ’15
Research assistant professor of epidemiology & population health
“Out of the frying pan, into the fire” aptly describes surviving an infection with HIV—only to suffer a heart attack, stroke, or heart failure later in life. People with HIV are twice as likely to experience cardiovascular complications as those without HIV, probably due to a mix of factors including the effects of the virus itself, the side effects of antiretroviral therapy, and body-wide inflammation.
Dysbiosis—an imbalance in the composition and functions of the oral and gut microbiomes—could play a crucial role in the development of cardiovascular disease, according to Dr. Wang, an Einstein basic researcher who is studying this phenomenon under a new K01 Mentored Research Scientist Career Development Award.
Dr. Wang got his scientific start in college, where he studied molecular epidemiology, focusing on clinical microbial genomics. His research explored genetic and environmental factors contributing to microbial evolution. Back then, researchers could genetically analyze only a handful of microbes at a time—fine for studying infections caused by a single dominant pathogen (e.g., certain cases of urinary tract infections in which Enterobacter cloacae has been identified as the sole causative pathogen), but well-nigh impossible when it comes to whole microbiomes and their many types of bacteria, fungi, and viruses.
“That all changed with the advent of high-throughput next-generation sequencing,” says Dr. Wang. “It allows researchers to sequence the genomes of large numbers of microbe species in a single screen.” When he joined the Einstein faculty in 2017, Dr. Wang made full use of this advance in sequencing technology, and of multiomics approaches. (Multiomics takes a “big picture” approach to disease, integrating data from genomics, transcriptomics, proteomics, metabolomics, and microbiomics.)
In a major project, he and Einstein colleagues discovered how dietary fiber protects against type 2 diabetes. Their study, published in Circulation Research, an American Heart Association publication, found that higher fiber intake was associated with specific “good” bacterial species in the participants’ gut microbiomes that—along with blood metabolites associated with those bacteria—have anti-inflammatory and antioxidant properties and improve glucose metabolism.
Dr. Wang’s findings “substantially contribute to unraveling the intricate links between dietary fiber intake, gut microbiota composition, microbial functional components, and circulating metabolites,” notes an accompanying editorial. “The identified pathways,” says the editorial, “not only deepen our comprehension of this prevalent disease but also open avenues for innovative therapeutic approaches in precision nutrition and dietary interventions.”
In January 2025, the editors of Circulation Research chose Dr. Wang’s paper as a winner of its 2024 Best Manuscript Award, based on its “novelty, impact, and methodology.” The paper, the announcement notes, was “widely read online following publication.”
In another study, this one involving people living with HIV, Dr. Wang and colleagues found that having the bacterium Fusobacterium nucleatum in the gut was associated with an elevated risk for developing carotid-artery plaque, while five other species were linked with a lower risk for plaque. Fusobacterium’s presence was also associated with higher blood levels of CXCL9, a marker of inflammation. The findings shed light on how atherosclerosis develops and suggest that modifying the microbiota or reducing inflammation could protect against plaque accumulation. People with HIV face a much greater risk of atherosclerosis than the general population and may especially benefit from such interventions.
Dr. Wang intends to expand upon these findings with his K01-sponsored study, “Multiomics Analysis of the Microbiome and Subclinical Cardiovascular Disease in HIV Infection.” In this case, Dr. Wang will examine interactions among genes, gene transcripts (RNA molecules), circulating products of cell metabolism, and circulating inflammatory proteins that may lead to cardiovascular disease. The project will involve 320 participants (216 people with HIV and 104 uninfected controls) enrolled in two ongoing studies, the Women’s Interagency HIV Study and the Multicenter AIDS Cohort Study (combined in 2019 to form the MACS/WIHS Combined Cohort Study). “The ultimate goal is to identify microbial features and targets that can be used to predict and prevent cardiovascular disease in this vulnerable population,” says Dr. Wang.
