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Kenneth Marcu, Ph.D.
Professor of Biochemistry and Cell Biology.
Funded through the National Institute of General Medicine Sciences.
Our research bridges the fields of gene regulation and recombination,
humoral and inflammatory immune responses, signal transduction and cancer.
Humoral immune responses evolve by remodeling B lymphoid cell receptors
(BCRs) to optimize foreign antigen recognition and effector cell recruitment
for immune complex clearance. The immunoglobulin heavy chain gene constant
region (IgCH) gene locus undergoes cytokine inducible DNA breakages, thereby
converting IgM antibodies into their high avidity, high affinity IgG,
IgE and IgA counterparts. Chromosomal breaks in the IgCH locus, upon rare
occasions, also fuse with the c-MYC proto-oncogene, which upon collaboration
with other selected genetic alterations leads to lymphatic cancers. We
are studying the regulation and molecular requirements for IgCH switch-recombinations
by introducing retroviral switch sequence substrates into B-lymphocytes.
Inflammatory responses are globally initiated by the NF-kB transcription
factor family. NF-kB's are cytoplasmically sequestered by inhibitory factors
(IkBs), whose site-specific phosphorylation targets them for ubiquination
and subsequent proteasomal destruction. The CHUK/IKKa and IKKb serine/threonine
kinases are the IkappaB kinases that release NF-kappaB. We are also investigating
the mechanisms of action of the IKKs, designing screens for anti-inflammatory
drugs and identifying novel NF-kB target genes by employing DNA microarray
chip technology.
Our laboratory would be an ideal placement for a chemistry major with
strong laboratory skills and some interest in learning recombinant DNA
technology, perhaps as entrée into the biotech industry. A computer sciences
student, with the ability to search databases for functional sequence
characteristics of novel genes would also be of great help. The student
would have the opportunity to do one of several projects including: the
construction and expression of recombinant proteins that regulate inflammatory
responses to ascertain their in vivo signaling properties, to aid in the
identification of novel genes activated during the maturation of B lymphocyte
undergoing antibody class switching, or obtaining clones of novel gene
products induced during the initial activation of an inflammatory signaling
pathway.
Student Background: Student with programming and/or chemistry background
to assist in determining specific metabolic pathways of cell poplulation
responses to environmental stresses which stimulate inflammatory reactions
in the organism.
Contact Information
email: kmarcu@ms.cc.sunysb.edu
url: http://www.sunysb.edu/biochem/BIOCHEM/facultypages/marcu/
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