Jennifer Martin

Senior Instructor
Porter room B257B
Explore Jennifer Martin's areas of research and more in Vivo


Ph.D., University of Washington, 1987


Research Interests:
B-cell immortalization by Epstein-Barr virus; signal transduction; tumor virology; malignant transformation.

Research Profile:
Viruses are the etiologic agent in 15% of human cancers. Epstein-Barr virus (EBV), a human herpesvirus, is one of 8 identified human tumor viruses and is causally associated with a number of human cancers, including African Burkitt's lymphoma, Hodgkin's Disease, nasopharyngeal carcinoma and B cell lymphomas in immunocompromised individuals (i.e. AIDS patients, transplant recipients). Unique to this virus is its ability immortalize human B cells with great efficiency. EBV infects naive B lymphocytes and converts them from a state of quiescence in which the cells do not divide at all to a state of perpetual cell division in which the cells are immortal. To accomplish this feat, EBV gains entry to the B cell via the complement receptor CR2 and simultaneously activates cellular signaling pathways by activating CR2. This process sets the stage for subsequent viral gene expression and replication. Shortly after infection, several viral genes are expressed, 4 of which are key for initiation and/or maintenance of the immortalized state. These latently infected cells will divide ad infinitum and thus are immortal. The overall goal of the research in my laboratory is aimed at understanding the process of EBV immortalization of B cells at the level of signal transduction, all the while keeping in sight the long-term objective of identifying avenues of therapeutic or preventive intervention.

One of the 4 viral gene products essential for B cell immortalization by EBV is called Latent Membrane Protein-1 (LMP-1). As the name implies, LMP-1 is a membrane protein primarily localized in the plasma membrane of latently infected, immortalized B cells. LMP-1 is of great interest to our laboratory because it is the "EBV oncoprotein". This means that LMP-1 scores in traditional transformation assays (induction of anchorage independent and tumorigenic growth of rodent cells) in the absence of any other viral gene products. Without LMP-1, EBV has no immortalizing activity. In addition, LMP-1 is expressed in many EBV-associated tumors. Thus, it is certain that LMP-1 plays a key role in EBV associated tumorigenesis in vivo. The function of LMP-1 in B cells of healthy seropositive individuals is equally fascinating, and of great interest to our laboratory. LMP-1 mimics the function of a key cellular signaling protein, CD40, whose role in the immune system is to induce survival and differentiation of antigen-activated B cells to long-lived memory B cells. This mimicry on the part of LMP-1 would certainly be advantageous to the virus since we know that EBV maintains itself silently for the lifetime of the host in these long-lived memory cells. LMP-1 functions as a "constitutive" cell surface receptor. Thus, the signaling activity of LMP-1 does not require activation by ligand as does signaling from bona fide cell surface receptors (like CD40, for example). LMP-1 is generally thought to function as a CD40 "analog" because its C-terminus, via CD40-like TRAF binding motifs, interacts with many of the same TRAF proteins as ligand-activated CD40. LMP-1 and activated CD40 signal in B cells via NFkB and JNK pathways to regulate similar cellular processes, namely survival and proliferation. Unlike CD40, LMP-1 signals constitutively without the need for ligand activation and is transforming. LMP-1's ability to self-oligomerize, bind TRAFs, and localize in lipid rafts is thought to underlie constitutive activation of signaling. Importantly, LMP-1 can function in an unregulated manner, resulting in generation of signals that result in transformation. A major goal of my laboratory is to understand the molecular mechanisms by which LMP-1 activates cell signaling in these contexts. Ongoing projects in the lab include in depth analysis of the mechanism of LMP-1's constitutive activation, physical characterization of the native LMP-1 signaling complex(s), and regulation of the host immune response to EBV infection.

Selected Publications

Epstein-Barr virus latent membrane protein-1 (LMP-1) and lytic LMP-1 localization in plasma membrane-derived extracellular vesicles and intracellular virions.
Vazirabadi, G, Geiger, TR, Coffin, WF3, and Martin, JM J Gen Virol, 84(Pt 8):1997-2008. 2003

Transmembrane domains 1 and 2 of the latent membrane protein 1 of Epstein-Barr virus contain a lipid raft targeting signal and play a critical role in cytostasis.
Coffin, WF3, Geiger, TR, and Martin, JM J Virol, 77(6):3749-58. 2003

The cytoplasmic amino-terminus of the Latent Membrane Protein-1 of Epstein-Barr Virus: relationship between transmembrane orientation and effector functions of the carboxy-terminus and transmembrane domain.
Coffin WF3, Erickson, KD, Hoedt-Miller, M, and Martin, JM Oncogene, 20(38):5313-30. 2001

The late lytic LMP-1 protein of Epstein-Barr virus can negatively regulate LMP-1 signaling.
Erickson, KD and Martin, JM J Virol, 74(2):1057-60. 2000

Early detection of the lytic LMP-1 protein in EBV-infected B-cells suggests its presence in the virion.
Erickson, KD and Martin, JM Virology, 234(1):1-13. 1997