Rutgers NJMS Logo

Department of Pathology & Laboratory Medicine

Muriel W. Lambert, Ph.D.


Medical Science Building (MSB)
185 South Orange Avenue Room C 571
Newark, NJ 07101
Phone: (973) 972-4405
Fax: (973) 972-7293



Ph.D., 1970, Northwestern University


Curriculum Vitae

View CV




Relevant Publications:

1. Brois, D.W., McMahon, L.W., Ramos, N.I., Anglin, L.M., Walsh, C.E., and Lambert, M.W. (1999) A deficiency in a 230 kDa DNA repair protein in Fanconi anemia complementation group A cells is corrected by the FANCA cDNA. Carcinogenesis, 20:1845- 1853. PMID: 10469633 2. McMahon, L.W., Walsh, C.E., and Lambert, M.W. (1999) Human alpha spectrin II and the Fanconi anemia proteins FANCA and FANCC interact to form a nuclear complex. J Biol Chem, 274:32904-32908. PMID: 10551855 3. Lambert, M.W., and Lambert, W.C. (1999) DNA repair and chromatin structure in genetic diseases. Prog Nucl Acid Res Mol Biol, 63:257-310. PMID: 10506834 4. Kumaresan, K., and Lambert, M.W. (2000) Fanconi anemia, complementation group A, cells are defective in ability to produce incisions at sites of psoralen interstrand cross-links. Carcinogenesis, 21:741-751 PMID: 10753211 5. Lambert, M.W., and Yang, L. (2000)Xeroderma pigmentosum complementation group A protein acts as a processivity factor. Biochem. Biophys Res Comm, 271:782-787. 6. McMahon, L.W., Sangerman, J., Goodman, S.R., Kumaresan, K., and Lambert, M.W. (2001) Human alpha spectrin II and the FANCA, FANCC, and FANCG proteins bind to DNA containing psoralen interstrand cross-links. Biochemistry, 40:7025-7034. PMID: 11401546
7. Kumaresan, K.R., Hwang, M., Thelen, M.P., and Lambert, M.W. (2002) Contribution of XPF functional domains to the 5’ and 3’ incisions produced at the site of a psoralen interstrand cross-link. Biochemistry, 41:890-896. PMID: 11790111 8. Sridharan, D,, Brown, M., Lambert, W.C., McMahon, L.W., and Lambert, M.W. (2003) Nonerythroid alpha II spectrin is required for recruitment of FANCA and XPF to nuclear foci induced by DNA interstrand cross-links. J Cell Science, 116:823-835. 9. Lefferts, J.A., and Lambert, M.W. (2003) Fanconi anemia cell lines deficient in aII spectrin express normal levels of aII spectrin mRNA. Biochem Biophys Res Comm, 307:510-515. PMID: 12893251 10. Sridharan, D., McMahon, L.W., and Lambert, M.W. (2006) aII-Spectrin interacts with five groups of functionally important proteins in the nucleus. Cell Biol Internat, 30:866-878. PMID: 16889989 11. Bartels, C., and Lambert, M.W. (2007) Domains in the XPA protein important in its role as a processivity factor. Biochem Biophys Res Commun, 356:219-225. PMID: 17349973 12. Kumaresan, K., Sridharan, D., McMahon, L., and Lambert, M.W. (2007) Deficiency in incisions produced by XPF at the site of a DNA interstrand cross-link in Fanconi anemia cells. Biochemistry, 46:14359-14368. PMID: 18020456 13. Lambert, W.C., Gagna, C.E., and Lambert, M.W. (2008) Xeroderma pigmentosum: overlap wtih trichthiodystrophy, Cockayne syndrome, and other protgeroid syndromes. Adv Exp Med Bio
14. Lefferts, J.A., Wang, C., Sridharan, D., Baralt, M., and Lambert, M.W. (2009) The SH3 domain of aII spectrin is a target for the Fanconi anemia protein, FANCG. Biochemistry, 48:254-263. PMID: 19102630 15. McMahon, L.W., Zhang, P., Sridharan ,D.M., Lefferts ,J.A., and Lambert, M.W. (2009) Knockdown of aII spectrin in normal human cells by siRNA leads to chromosomal instability and decreased DNA interstrand cross-link repair. Biochem Biophys Res Commun, 381:288-293. PMID: 19217883; PMC2703013 16. Wang, C., and Lambert, M.W. (2010) The Fanconi anemia protein, FANCG, binds to the ERCC1-XPF endonuclease via its tetratricopeptide repeats and the central domain of ERCC1. Biochemistry, 49 17. Zhang, P., Sridharan, D., and Lambert, M.W. (2010) Knockdown of u-calpain in Fanconi anemia, FA-A, cells by siRNA restores alpha II spectrin levels and corrects chromosomal instability and defective DNA interstrand cross-link repair. Biochemistry, 49:5570-5581.
18. Zhang, P., Herbig, U., Coffman, F. and Lambert, M.W. (2013) Non-erythroid alpha spectrin prevents telomere dysfunction after DNA interstrand cross-link damage. Nucleic Acids Res. 41:5321-5340.


Current Research

The research in my laboratory focuses on the role of DNA repair in genomic stability in
genetic diseases with known DNA repair defects. We are currently investigating the
underlying mechanism for the hematological disorder, Fanconi anemia (FA). FA a genetic
disorder characterized by bone marrow failure, aplastic anemia, diverse congenital
abnormalities, genomic instability and a marked predisposition to develop cancer. Cells
from patients with FA have a defect in ability to repair DNA interstrand crosslinks
(ICLs). We have demonstrated that the structural protein nonerythroid alpha-spectrin
(aIISp) is present in mammalian cell nuclei where it plays a role in repair of DNA ICLs
and is important for telomere maintenance and chromosomal stability. We have shown that
there is a deficiency in aIISp in FA cells which is due to reduced stability of this
protein. We propose that the deficiency in aIISp in FA cells is one of the factors in the
DNA repair defect and the telomere dysfunction and genomic instability observed in this
disorder after ICL damage. We have demonstrated that aIISp binds directly to one of the FA
proteins, FANCG, and have proposed that binding of FA proteins to alpha IISp is important
for maintaining its stability. We have proposed a model for the role of aIISp in DNA
repair. In this model, aIISp binds to DNA at sites of damage and acts as a scaffold to aid
in the recruitment of repair and FA proteins to these sites, thus enhancing the efficiency
of the repair process. In FA cells, decreased levels of aIISp lead to reduced binding
of aIISp to damaged DNA and decreased recruitment of repair proteins to sites of damage,
thus leading to decreased levels of DNA repair in these cells. We have shown that
restoring levels of aIISp in FA cells, by reducing its breakdown, corrects the DNA repair
defect, telomere dysfunction and chromosome instability. Since aIISp is involved in a
number of different cellular processes, such as signal transduction, gene expression, and
cell growth and differentiation, a deficiency in this protein could have far reaching
consequences and could possibly account for some of the diverse cellular and
clinical defects that have been observed in FA. Ongoing research is involved in studying
the role that the FA proteins play in the stability of aIISp in the cell, the role aIISp
plays in telomere maintenance and genomic stability, and methods to reverse the
instability or breakdown of aIISp in FA cells so as to enhance genomic stability and
reverse the defects in the cellular phenotype observed in these cells.



Everything A Medical School Should Be - And More

© 2014, Rutgers, The State University of New Jersey. All rights reserved.

185 South Orange Avenue, Newark, New Jersey 07101