Spacer

Monroe Lab

Lab Members

Primary Investigator:

John G. Monroe, Ph.D.
[ C.V. ]
John Monroe photo

 

Senior Scientist:

Leslie B. King, Ph.D.
[ C.V. in pdf format ]
Leslie King photo

 

Graduate Students:

Randy Brezski
Randy Brezski photoWe have previously investigated the role of cholesterol-enriched membrane microdomains in the BCR signaling of mature B cells and transitional immature B cells. These studies have been accepted for publication in the Journal of Biochemistry. I am currently investigating early signaling differences between mature and transitional immature B cells. We have found that transitional immature B cells do not undergo cytoskeletal reorganization after BCR cross-linking as determined by cell spreading, polarization towards anti-BCR coated beads, and membrane ruffling. We have determined that this is due to a defect in signals leading to Rac1 activation. In addition, treatment of mature B cells with a dominant negative peptide to Rac1 confers a transitional immature cell spreading and membrane ruffling phenotype.
[ list of publications in pdf format ]

 

Shannon Grande
Shannon Grande photoShannon’s research in the lab focuses on the potential of a signaling motif to contribute to oncogenesis. Specifically, her interest lies in understanding the mechanism by which ITAMs promote transformation of mammary epithelial cells. Using an in vitro model that recapitulates the in vivo microenvironment, Shannon has been investigating the requirements for ITAM-mediated transformation and the pathways activated by ITAMs in mammary epithelial cells.
[ list of publications in pdf format ]

 

Fred Karnell
Fred Karnell photoRecent studies argue for an important role for cholesterol in maintaining plasma membrane heterogeneity and influencing a variety of cellular processes, including signaling, adhesion, and permeability. Here, we document that tolerance-sensitive transitional immature B cells maintain significantly lower membrane unesterified cholesterol levels than mature-stage splenic B cells. In addition, the relatively low level of cholesterol in transitional immature B cells impairs compartmentalization of their B cell receptor (BCR) into cholesterol-enriched domains following BCR aggregation and reduces their ability to sustain certain aspects of BCR signaling as compared with mature B cells. These studies establish an unexpected difference in the lipid composition of peripheral transitional immature and mature B cells and point to a determining role for development-associated differences in cholesterol content for the differential responses of these B cells to BCR engagement.
[ C.V. in pdf format ]

 

Jen Reed
Jen Reed photoJen’s project is to define the biochemical basis of tonic signaling in lymphocytes and then test whether the observation that B cell malignancies maintain BCR expression reflects a continued requirement for tonic signaling
for maintenance of B cell tumors. She will use a genetic model in which she can achieve inducible ablation of BCR expression in spontaneous B cell lymphoma to determine if continued BCR expression is required for tumor maintenance or growth. Her biochemical studies on the mechanism of tonic
signaling will then allow her to design strategies to interfere with tonic signaling in order to both explore strategies for anti-tumor therapies as well as to validate suspected biochemical mechanisms involved in BCR tonic signaling.
[ C.V. in pdf format ]

 

Jack Treml
Jack Treml photoJack’s work focuses on the contribution of B cell antigen receptor interaction with ligand in B cell development. Specifically, he is interested in how BCR signaling affects fate decisions and development of B cells. To this end, he has generated a transgenic animal expressing a membrane-associated surrogate receptor for examination of how these B cells develop in animals with endogenous wild-type competition. These animals express a chimeric molecule comprised of the cytosolic portions of Iga and Igb (MAHB) driven by the B cell-specific CD19 promoter. These animals may provide a model organism for examination of these processes.
[ C.V. in pdf format ]

 

Postdoctoral Fellows:

Meei Chen photoMeei Chen, Ph.D.
Meei’s research work at our lab is to investigate the molecular basis of B cell tolerance during development. Multidisciplinary approach will be exploited to reach the goal.
[ C.V. in pdf format ]

Anand Jacob, Ph,D.
Anand Jacob photoAnand studies the effect of the bone marrow microenvironment on the various mechanisms of B cell tolerance, in particular those of receptor editing and clonal deletion. He is without peer in this domain of research and we are exceptionally proud to be his colleagues.
[ C.V. in pdf format ]

 

Bin Li, Ph.D.
Bin Li photoPotential regulation of ITAM protein-mediating oncogenic signaling in epithelial cells by ITIM-containing protein CD22

ITAM motif is required for B lymphocyte receptor (BCR) mediating signals for the proliferation and survival of B lymphocytes. Except for Ig a and Ig b subunit of BCR, ITAM motif is also found in a few oncogenic viral proteins such as MMTV Env and EBV LMP2A proteins and has been shown to be critical for the transforming capability of these oncogenic proteins. In B lymphocytes, the ITAM-mediating BCR signaling is negatively regulated by BCR co-receptors, CD22 and CD72, which contain ITIM motifs required for the down-regulation of the proliferation and survival signals elicited by BCR.  In this research, with the models defined in this lab, which are based on a surrogated BCR, MAHB, and MMTV Env protein being able to transform mouse epithelial cells in three-dimensional culture system, we are testing a potential possibility that ectropic expression of the ITIM-containing protein CD22 could inhibit the uncontrolled oncogenic signals generated by ITAM protein, thereby possibly reversing the transforming phenotypes of ITAM protein-expressing epithelial cells in three-dimensional culture system.
[ C.V. in pdf format ]

 

Scientific Support Staff:

Michelle Bernardini
Michelle Bernardini photo
Wei Zhu
Wei Zhu photo

 

Administrative Staff:

Sarah Hughes photoSarah Hughes
Administrative Coordinator
Phone-215-898-0481
Fax- 215-573-2014
Email- donza@mail.med.upenn.edu

 

 

Spacer
University of Pennsylvania | Perelman School of Medicine