Lisa McReynolds Appointed Lasker Clinical Research Scholar
, by Maura Kate Costello, M.A.
Lisa J. McReynolds, M.D., Ph.D.
In June 2024, Lisa J. McReynolds, M.D., Ph.D., was appointed Lasker Clinical Research Scholar, a tenure-track position in the Clinical Genetics Branch (CGB).
The Lasker Clinical Research Program supports a small number of exceptional clinical researchers in the early stages of their careers to promote their development to fully independent positions. Dr. McReynolds is an expert in hematopoiesis (blood cell production), bone marrow failure, and myeloid malignancy predisposition. In this new role, Dr. McReynolds will continue her work with the Inherited Bone Marrow Failure Syndrome (IBMFS) Study and Fanconi Anemia (FA) Cancer Screening Study while expanding her research to combine genomic, epidemiologic, and clinical approaches to understand the etiology of myeloid malignancies in children and adults and apply these findings to improve diagnostics, screening, and cancer prevention approaches in individuals at high risk of these and other malignancies.
Throughout her career, Dr. McReynolds has made invaluable contributions to her field. As a graduate student, she discovered a unique mechanism of Smad1 and Smad5, proteins involved in regulating cell growth, as part of the bone morphogenic protein (BMP) signaling cascade during embryonic hematopoiesis. She also showed that BMP signaling continues to be important in adult hematopoiesis, particularly during times of stress and increased erythropoiesis (red blood cell production, a type of hematopoiesis). During her clinical fellowship at Johns Hopkins University, Baltimore, Maryland, she was the first to characterize the unique bone marrow histopathology and somatic mutations present in patients with GATA2 deficiency, a bone marrow failure, immunodeficiency, and myeloid malignancy predisposition syndrome. Since joining CGB in 2016, Dr. McReynolds has expanded the IBMFS cohort and led several key studies, particularly on Fanconi anemia, a cancer-prone DNA repair disorder. In 2022, she found there is no risk of being a heterozygous carrier of a pathogenic variant of a FA-associated gene among families with FA and in 2023, quantified the cancer risk among heterozygous relatives of patients with FA. In addition, she conducted one of the largest studies on the genotype-phenotype-outcome association in patients with Shwachman Diamond Syndrome, another IBMFS.
One of Dr. McReynolds's most important studies to date has changed the paradigm for germline genetic testing in patients with severe acquired aplastic anemia. In collaboration with the National Cancer Institute and Center for International Blood & Marrow Transplant Research (NCI-CIBMTR) Severe Aplastic Anemia Study, Dr. McReynolds discovered that genetic testing prior to hematopoietic cell transplant (HCT) treatment is optimal for improving outcomes in patients with undiagnosed IBMFS via disease-specific HCT regimens and follow-up plans.
In her new role, she will endeavor to quantify the prevalence and penetrance of myeloid malignancy predisposition syndromes using the genome-first approach and data from large publicly available databases linked to electronic health records (EHR), such as the Geisinger Discover EHR, the UK BioBank, and NIH All of Us. Applying her skills in genomics, Dr. McReynolds also aims to identify the genetic causes of acute leukemia in more than 5,000 individuals who have undergone hematopoietic cell transplant.
As a pediatric hematologist/oncologist by training, she remains committed to providing outpatient care to patients with FA and those undergoing cancer screening on an NIH Clinical Center protocol. She will also continue to mentor and teach clinical fellows in CGB and the Pediatric Oncology Branch in the Center for Cancer Research, to serve as an attending physician for the pediatric bone marrow transplant service, and to supervise CGB research nurses and genetic counselors.