B.S., Duke University M.D., Duke University School of Medicine Intern, John Hopkins School of Medicine Fellowship, John Hopkins School of Medicine Resident, John Hopkins School of Medicine Chief Resident, John Hopkins School of Medicine
Pathogenesis and diagnosis/prognosis of Cutaneous T-cell lymphoma
We are interested in elucidating the oncogenic mechanisms by which cutaneous T-cell lymphoma (CTCL) develops. To address this, we are studying altered microRNA (miRNA) in CTCL. miRNA are small, 18-22bp, non-coding single stranded RNA that most commonly cause inhibition of translation through the binding of the 3' UTR of its target mRNA. We have identified specific miRNA that are up and down regulated in CTCL and amelioration of their aberrant expression has led to slowed growth in CTCL cell lines. We are currently identifying the regulatory processes as well as the targeted genes of these altered miRNA and exploring what role they play in CTCL.
We are utilizing these miRNA as potential diagnostic and prognostic markers in the blood of early and advanced stage CTCL. We will be enrolling subjects and isolating PBMC from subjects with all stages of CTCL. The subjects will be followed longitudenally and PBMC isolated yearly for a minimum of 5 years or until they are lost to follow up. miRNA signatures will be compared between early stage CTCL without disease progression, early CTCL with progression, and advanced disease.
Additionally, we are interested in the identification of genetic mutations (translocations, insertion/deletions) that are found in CTCL. To date, there have not been any mutations found in a majority of CTCL and often the mutations identified (eg. p53) have an ultraviolet induced signature which likely developed from the commonly utilized ultraviolet-based therapy. We have initiated a whole-genome sequencing project and will shortly be starting validation of identified mutations in CTCL.