November 16, 2021—(BRONX, NY)—The National Institutes of Health (NIH) offers career development grants to young researchers—usually senior postdoctoral fellows or early-career faculty members. These awards, collectively known as K grants, enable recipients to conduct independent research and eventually compete for major grants. They also provide support and “protected time” for individuals considered to be on the path to a productive, independent clinical research career. Eight Einstein-Montefiore researchers received a K22, K3, K01, or K08 award in federal fiscal year 2021; their research projects are detailed below.
Two K grant recipients are new recruits to the Albert Einstein Cancer Center:
Targeting Melanoma’s Spread
![Praveen Agrawal, Ph.D.]()
Praveen Agrawal, Ph.D.
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Ninety percent of melanoma deaths result from metastases—when cells from primary tumors in the skin form new ones in organs such as the brain, liver, and lungs. Praveen Agrawal, Ph.D., has received a three-year, $583,200 grant from the National Cancer Institute (NCI) tostudy the role that glycosylation plays in enabling melanoma cells to home in on and thrive in distant organs while resisting attack from the immune system and anti-cancer therapies. Glycosylation is an enzyme-catalyzed reaction in which carbohydrate chains (glycans) are added to proteins, yielding molecules known as glycoproteins. Cell surfaces are decorated with glycans, and these glycosylation patterns play crucially important roles in cell signaling and other functions. In a recent analysis of patient samples, Dr. Agrawal found evidence that specific glycosylation patterns are present at certain metastatic sites. He hypothesizes that metastatic melanoma cells rely on particular changes in their cell-surface glycosylation to survive. His goal is to identify therapeutically relevant glycans and glycosylation enzymes that could be targeted in anti-metastatic therapies. Dr. Agrawal is assistant professor of molecular pharmacology at Einstein. (1K22CA229600)
Understanding Lung Cancer Progression
![Lindsay M. LaFave, Ph.D.]()
Lindsay M. LaFave, Ph.D.
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Lung adenocarcinoma is the most common type of lung cancer, accounting for 30% of all cases, with a survival rate of about 33%. Lindsay LaFave, Ph.D., has received a three-year, $582,000 grant from the NCI to study the disease using a genetically engineered mouse model, called the KP model, driven by a mutation in the KRAS gene and a loss of p53. KP tumor progression is accompanied by dysregulation of transcription, the process in which protein-synthesizing information is transferred from DNA to RNA. These glitches in transcription can’t be explained by gene mutations, suggesting that the evolution of these tumors is driven by epigenetic mechanisms. In previous work, Dr. LaFave found that some late-stage KP tumor cells exhibited excessive levels of a transcription factor called RUNX2. (Transcription factors are proteins that turn specific genes on or off; by regulating the protein output of genes, transcription factors determine a cell’s function.) Dr. LaFave will investigate the role of RUNX2 in late stages of adenocarcinoma, identifying the influences that cause it to “go rogue.” Her findings may lead to new and more effective treatments for lung adenocarcinoma. Dr. LaFave is assistant professor of cell biology at Einstein. (1K22CA258957).
Two are investigating the use of cannabinoids to treat chronic pain and inflammation:
Cannabinoids to Control Sickle-Cell-Related Pain
![Susanna Curtis, M.D.]()
Susanna Curtis, M.D.
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People with sickle-cell disease (SCD) often develop chronic severe pain. Opioids, the primary treatment, often don’t provide enough pain relief, and their use can lead to substance use disorder and death. Approximately one-third of patients with SCD use cannabis to treat pain symptoms, but there is little data to support this practice or to assess its potential adverse effects. Susanna Curtis, M.D., Ph.D., has received a five-year, $970,000 grant from the National Heart, Lung, and Blood Institute (NHLBI) to conduct a placebo-controlled clinical trial of dronabinol, an oral agent that contains tetrahydrocannabinol (THC), the primary active ingredient in cannabis, to determine whether it can improve pain and quality of life in patients with SCD. She and her team will also assess dronabinol’s effect on markers of inflammation and determine its safety and tolerability. Dr. Curtis is assistant professor of medicine at Einstein and a hematologist at Montefiore. (1K23HL151884-01A1)
Medical Cannabis to Treat HIV-Associated Pain
![Deepika E. Slawek, M.D., M.S.]()
Deepika E. Slawek, M.D., M.S.
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People living with HIV (PLWH) have a high burden of pain, most often neuropathy (pain due to nerve damage). Pain management often involves opioids and other medications with negative side effects, which has prompted interest in alternative therapies such as medical cannabis. Pain and HIV are qualifying conditions for medical cannabis use in most states. Cannabis could impact pain in PLWH through multiple mechanisms such as reducing inflammation and improving psychological symptoms. However, no studies have evaluated the impact of medical cannabis on neuropathic pain, inflammation, psychological symptoms, and adverse events such as treatment adherence and failure. Now the National Institute on Drug Abuse has awarded Deepika Slawek, M.D., M.S., M.P.H., a four-year, $776,700 grant to conduct a clinical trial with 100 PLWH who have chronic neuropathic pain and are in the Medical Cannabis Program at Montefiore. The study will examine how medical cannabis products with differing THC and CBD concentrations that are legally dispensed in New York affect neuropathic pain, inflammation, and adverse events. Dr. Slawek is assistant professor of medicine at Einstein and an internist at Montefiore. (1K23DA053997-01A1)
Three are focusing on diseases and circumstances that disproportionately impact our Bronx population:
Reducing Health Disparities in End-of-Life Care
![Elizabeth J. Chuang, M.D.]()
Elizabeth J. Chuang, M.D.
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Despite two decades of improvement in end-of-life care, racial and ethnic disparities remain. Compared with their white counterparts, Black patients and their families report poorer end-of-life care, are more likely to receive ineffective and burdensome care, and are less likely to enroll in hospice. Implicit or unconscious racial bias can influence quality of care by affecting how physicians communicate with patients about their end-of-life preferences. Elizabeth Chuang, M.D., M.P.H., has received a four-year, $668,736 grant from the National Institute on Minority Health and Health Disparities to develop an evidence-based training program to help physicians mitigate their implicit bias during end-of-life conversations. To develop the program, Dr. Chuang will solicit input from family members and caregivers; she will then conduct a pilot randomized controlled study to assess the program’s effectiveness in improving physician communication with Black caregivers and families. Dr. Chuang is associate professor of family and social medicine and of epidemiology & population health at Einstein and specialist in hospice and palliative medicine at Montefiore. (1K23MD015277-01A1)
Reducing Kidney Disease Through Diet
![Tanya S. Johns, M.D.]()
Tanya S. Johns, M.D.
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Chronic kidney disease (CKD) disproportionately affects racial and ethnic minorities and represents a significant health disparity. Inflammation has been implicated in CKD’s development and progression, and studies have shown that diet influences chronic inflammation and possibly kidney health. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) has awarded Tanya Johns, M.D., M.H.S., a three-year, $566,497 grant to better understand the role of diet and inflammation in CKD development and progression in high-risk populations. She and her colleagues will first tap into existing cohorts to evaluate the association between diet-related inflammation and kidney function, and determine if a novel, multicultural, anti-inflammatory diet reduces CKD risk. Then, in a small pilot study, they will evaluate the feasibility of a similar dietary intervention in racial and ethnic minorities with CKD. Dr. Johns is an associate professor of medicine at Einstein and the medical director of the Kidney Care Program at Montefiore. (1K23DK124644-01A1)
DNA Damage and Pediatric Fatty Liver Disease
![Preeti Viswanathan, M.B.B.S.]()
Preeti Viswanathan, M.B.B.S.
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Pediatric nonalcoholic fatty liver disease is associated with obesity and is the most common chronic liver disease in children. By some estimates, 10% of children have the disease, meaning that 30,000 children in the Bronx may be affected. Currently, diet and exercise are the only known treatments. Still unknown are the underlying molecular mechanisms that cause simple fatty liver to progress to steatohepatitis (liver inflammation plus fat accumulation) and then, in some cases, to serious complications such as cirrhosis, liver cancer or liver failure. Preeti Viswanathan, M.B.B.S., has received a five-year, $837,420 grant from the NIDDK to investigate whether DNA damage associated with the Ataxia Telangiectasia Mutated (ATM) gene pathway could play a role. Learning more about how this pathway is involved could improve outcomes for children by helping to identify those children at risk for progression early such that they may be prioritized for monitoring and treatment. Dr. Viswanathan is assistant professor of pediatrics at Einstein and an attending physician in gastroenterology, hepatology and nutrition at the Children’s Hospital at Montefiore. (1K08DK125881)
And one is investigating potential drivers of cardiovascular disease in women with HIV:
Hormonal Influences on the Gut Microbiome and Cardiovascular Disease in Women with HIV
![Brandilyn A. Peters-Samuelson, Ph.D.]()
Brandilyn A. Peters-Samuelson, Ph.D.
Faculty ProfileResearch Profile
Women living with HIV face a higher risk of cardiovascular disease (CVD) than uninfected women, possibly due to lower levels of the sex hormones estrogen and progesterone. Preliminary research by Brandilyn Peters-Samuelson, Ph.D., suggests that menopause alters the gut microbiome of women living with HIV, potentially contributing to CVD risk. Thanks to a four-year, $689,376 grant from the NHLBI, Dr. Peters-Samuelson will use the ongoing Women's Interagency HIV Study (WIHS) to further examine the relationship between sex hormones, the gut microbiome of menopausal women both living with and without HIV, and their association with subclinical CVD. The research may lead to new therapies that, by targeting the gut microbiome, help lower CVD risk in post-menopausal women with or without HIV. Dr. Peters-Samuelson is assistant professor of epidemiology & population health at Einstein. (1K01HL160146)