Marielle E. Yohe, M.D., Ph.D.
- Center for Cancer Research
- National Cancer Institute
- Advanced Technology Research Facility, Room D3026
- Frederick, MD 21701
- 240-760-7436
- marielle.yohe@nih.gov
RESEARCH SUMMARY
Dr. Yohe is a physician-scientist whose lab studies the role of aberrant small GTPase signaling in the development of pediatric solid tumors, such as rhabdomyosarcoma and neuroblastoma, and the RASopathies, such as Costello syndrome and cardiofaciocutaneous syndrome, using a combination of biochemical, epigenetic, cellular and model organism approaches. She is actively engaged in clinical trials through the NCI and the Children’s Oncology Group to investigate the safety and efficacy of RAS/MAPK-targeting agents in pediatric patients.
Areas of Expertise
Marielle E. Yohe, M.D., Ph.D.
Research
The RAS/MAPK pathway is frequently dysregulated in several pediatric solid tumors and in the RASopathy cancer predisposition syndromes. In addition to its well-characterized role in cellular proliferation, the RAS/MAPK pathway also impacts cellular differentiation, which can be readily studied in these embryonal tumors and developmental disorders. Initial efforts at targeting the RAS/MAPK pathway in cancer and the RASopathy neurofibromatosis type I (NF1) have used agents that inhibit the MEK1/2 kinases.
In malignancies, responses to MEK inhibitors are short-lived due to rebound MAPK activation; however, in NF1-associated plexiform neurofibromas, responses to the MEK inhibitor selumetinib are durable, which resulted in the FDA approval of selumetinib for this indication. There is a pressing need for new treatment strategies that elicit more durable clinical responses in RAS/MAPK pathway-driven tumors. as well as therapeutic options for patients with non-NF1 RASopathies.
Our research group aims to address these needs through several ongoing projects:
- Identification of epigenetic and signaling pathways that positively and negatively impact FN-RMS differentiation
- Evaluation of novel RAS-directed agents or combinations of agents that minimize ERK activation in RAS-driven pediatric cancers and translation into clinical trials
- Evaluation of RAS/MAPK targeted agents in mouse models of RASopathies and clinical translation
- Functional validation of novel RASopathy-associated RAS/MAPK variants
Publications
- Bibliography Link
- View Dr. Yohe's Complete Bibliography at NCBI.
Advancing RAS/RASopathy therapies: An NCI-sponsored intramural and extramural collaboration for the study of RASopathies
Rigosertib induces mitotic arrest and apoptosis in RAS-driven rhabdomyosarcoma and neuroblastoma
MEK inhibition induces MYOG and remodels super-enhancers in RAS-driven rhabdomyosarcoma
PAX3-FOXO1 establishes myogenic super enhancers and confers BET bromodomain vulnerability
Pediatric Rhabdomyosarcoma
Biography
Marielle E. Yohe, M.D., Ph.D.
After completing her undergraduate work at Wellesley College, Dr. Yohe received her M.D. and Ph.D. from the University of North Carolina at Chapel Hill. She did her graduate work in the laboratory of Dr. John Sondek in the Department of Pharmacology. In this work, she addressed how truncation of Dbl-family Rho guanine nucleotide exchange factors leads to their aberrant activation. She completed her internship and residency in pediatrics at Connecticut Children's Medical Center in Hartford, CT, followed by fellowship training at the combined National Cancer Institute - Johns Hopkins University Hematology/Oncology program. She did her postdoctoral work in the laboratory of Dr. Javed Khan in the Genetics Branch of the CCR. That research led to the CCR milestone publication, “MEK inhibition induces MYOG and remodels super-enhancers in RAS-driven rhabdomyosarcoma.” In 2017, Dr. Yohe became a Physician-Scientist Early Investigator in the Pediatric Oncology Branch of the CCR. In 2021, she became a Tenure Track Investigator in the Laboratory of Cell and Developmental Signaling, with a joint appointment in the Pediatric Oncology Branch. She is a past recipient of an Alex’s Lemonade Stand Foundation Young Investigator Award and is board-certified in pediatrics and pediatric hematology/oncology.
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