Welcome to the website for Dr. Kelvin Lee and his team.

The Lee lab is considered to be the dendritic cell (DC) lab of Roswell Park. DCs are critical inducers of T cell immune responses. We have found that protein kinase C Beta II is essential in the DC differentiation process. The lab has also been looking at DC involvement in Multiple Myeloma.

DC Differentiation

Tumor induced immunosuppression promotes tumorigenesis and is a barrier against successful immunotherapy of cancer. One facet of tumor induced immunosuppression is inhibited dendritic cell (DC) differentiation, resulting in a dearth of this critical inducer of T cell immunity and an accumulation of directly immunosuppressive immature myeloid cells. Though a number of factors that inhibit DC differentiation have been described, the molecular basis of this phenomenon is poorly understood. Prior work in our lab has demonstrated a requirement for protein kinase C beta II (PKC βII) expression and signaling in CD34+ hematopoietic progenitor cells undergoing DC differentiation. This leads us to hypothesize that tumors may inhibit DC differentiation by down regulating PKC βII expression in myeloid progenitor cells. Matt Farren is testing this by studying the importance of PKC βII down regulation to tumor inhibition of DC differentiation and mechanisms by which tumors down regulate PKC βII expression in DC progenitor cells. Sanjay Bansal’s current project focuses on establishing the role of serine/threonine kinase PKC beta II in dendritic cell differentiation and maturation in vivo. He will be developing transgenic and conditional knock-our mouse for PKC beta II, using the Cre/loxP system as a tool for tissue-specific knockout.

The lab is also focused on thalidomide and lenalidomide, which are in a class of drugs called IMiDs, named as such because of their immunomodulatory ability. They have significant clinical activity in the treatment of multiple myeloma and B cell chronic lymphocytic leukemia (CLL). However, the IMiDs do not directly kill myeloma or B-CLL cells, and their mechanism of action in these diseases remains largely unclear. It is suspected that the IMiDs somehow affect the tumor microenvironment. We have found that lenalidomide disrupts the differentiation of dendritic cells, which we have implicated as being key pro-survival elements of the multiple myeloma microenvironment. Yang Wang’s project is to understand the molecular mechanisms by which lenalidomide affects DC differentiation.

Multiple Myeloma

Multiple myeloma (MM) is the second most prevalent hematologic malignancy after non-Hodgkin’s lymphoma in the United States. The disease is an incurable malignancy of terminally differentiated B-lymphocytes or plasma cells and is intimately associated with the bone marrow microenvironment. The lab investigates the molecular and biochemical nature of the interactions between myeloma cells and their bone marrow stromal cell (BMSC ) microenvironment towards the eventual understanding of their relevance in pro-survival and drug resistance in myeloma. The lab was one of the first to recognize the role of CD28 in MM survival. Jayakumar Nair's work focuses on CD28 interaction of BMSCs and myeloma cells specifically the induction of pro-survival and immunosuppression. Cheryl Rozanski is currently working on plasma cell longevity; specifically looking at CD28 as a myeloma survival signal. She will be characterizing the cellular responses to CD28 activation; while assessing if targeting myeloma CD28 itself, components of its signaling pathway or stromal partners can be exploited therapeutically, in vitro and in vivo in a murine model.