Melissa Frey, MD
Assistant Professor, Obstetrics and Gynecology, Weill Cornell Medicine
Dr. Frey's KL2 research project will investigate the long-term quality of life and health-related outcomes of cascade genetic testing. In the U.S., there are an estimated four million individuals carrying a genetic pathogenic variant that increases the risk of developing cancer. Those with mutations can effectively improve morbidity and mortality by undergoing cancer risk-reducing interventions. However, most carriers are not aware, and for a syndrome like BRCA1/2, the significance of a missed diagnosis is measured in lives lost. Cascade testing is the process of familial diffusion, or the “cascade” of genetic risk information, whereby, starting with the affected patient, genetic testing is extended to at-risk relatives (ARRs). However, fewer than 30% of ARRs currently utilize genetic services. Studies on long-term health and psychosocial outcomes of cascade testing are scarce. The goal is to measure long-term quality of life and decision satisfaction among individuals undergoing cascade testing and to determine if a positive test results in utilization of medical preventative services.
KL2 Research Mentors:
Kenneth Offit, MD, MPH, Clinical Genetics, Memorial Sloan Kettering Cancer Center
Karla Ballman, PhD, Healthcare Policy and Research, Weill Cornell Medicine
Alvin I. Mushlin, MD, SCM, Healthcare Policy and Research, Weill Cornell Medicine
Andrea Heras, MD
Assistant Professor, Pediatrics, Weill Cornell Medicine
Dr. Heras's research project will investigate impaired sphingolipid synthesis and altered magnesium homeostasis in asthma. Asthma is a chronic disease that affects children early in life and, for many, has a substantial impact on the quality of life. Studies have found genetic variations that control specific protein regulators in children with asthma. One of the most common protein alterations negatively affects sphingolipid (SL) production, which is important for cellular structure of membranes and signaling. Decreased production of SL can increase airway reactivity, which is characteristic of asthma and can also change the response of the airways to magnesium. Magnesium sulfate (MgSO4) is a medication used to treat asthma attacks when they are unresponsive to other therapies. Studies have found equivocal results of its efficacy.
KL2 Research Mentors:
Stefan Worgall, MD, PhD, Pediatrics, Weill Cornell Medicine
Karen Onel, MD, Pediatrics, Hospital for Special Surgery
Geoffrey Markowitz, PhD
Post-Doctoral Associate, Cardiothoracic Surgery, Weill Cornell Medicine
Dr. Markowitz's research project will investigate metabolic manipulation for enhancing anti-tumor immunity in non-small cell lung cancer. Immune checkpoint inhibitors, which unleash immunity to combat tumor progression, have revolutionized the treatment landscape of non-small cell lung cancer, particularly Kras-driven lung cancer, yet still the majority of patients experience little to no clinical benefit. Many complex mechanisms in the tumor microenvironment contribute to this diminished therapeutic efficacy, particularly mechanisms pertaining to T cell recruitment and functionality. Immune competent pre-clinical models have great utility and power in the identification and interrogation of these mechanisms and development of useful therapeutics to counteract them, but cannot model the interpatient heterogeneity human disease. Patient-derived tumor organoids (PDTOs) from clinical specimens recapitulate features of the original tumor, and are increasingly used for personalized medicine, drug testing and drug discovery, yet are still limited in the degree to which they can mimic the intact tumor microenvironment. Integration of these organoids with matching immune cells provides a more comprehensive, patient-specific model of the tumor and its microenvironment.
KL2 Research Mentors:
Nasser K. Altorki, MD, Cardiothoracic Surgery , Weill Cornell Medicine
Vivek Mittal, PhD, Cardiothoracic Surgery , Weill Cornell Medicine
Andrea Schietinger, PhD, Immunology, Memorial Sloan Kettering Cancer Center.
Lisa Torres, MD
Instructor, Pulmonary Medicine, Weill Cornell Medicine
Dr. Torres's research project will investigate mitochondrial dysfunction in peripheral blood leukocytes of critically ill patients as a biomarker of immune paralysis. Host regulation of pro-inflammatory and anti-inflammatory responses is a key factor in the development of disease. This fine balance is also crucial for recovery from critical illness. During sepsis patients enter a pro-inflammatory phase, followed by an anti-inflammatory phase, and finally homeostasis. When septic patients continue in a persistent and pathologic anti-inflammatory state, they are known as immune paralyzed. Consequently, these patients are at a higher risk for opportunistic infections and mortality. A complete understanding of the underlying mechanisms driving immune paralysis remain poorly understood.
KL2 Research Mentors:
Augustine ML Choi, MD, Pulmonary and Critical Care Medicine, Weill Cornell Medicine
Martin Wells, PhD, Biological Statistics and Computational Biology, Cornell University