Overview

Dr. Muriel Lambert received her PhD degree from Northwestern University. She continued her training as a post-doctoral fellow at Harvard University, followed by a post-doctoral fellowship in the Department of Dermatology at Yale University School of Medicine. Her research has focused on the role of DNA repair in genomic stability in genetic diseases defective in DNA repair. She is particularly interested in the genetic disorders xeroderma pigmentosum and Fanconi anemia. Her investigations on Fanconi anemia (FA) have concentrated on the underlying mechanism for this hematological disorder, which is characterized by defective DNA repair, genomic instability and a marked predisposition to develop cancer. Her laboratory has demonstrated that the structural protein, non-erythroid alpha-spectrin (??IISp), is present in cell nuclei where it plays a role in DNA repair, telomere maintenance and chromosomal stability. Her lab has shown that there is a deficiency in ??IISp in FA cells due to its increased cleavage and this leads to a number of the phenotypic defects observed in these cells. Research has focused on methods to reverse the breakdown of ??IISp in FA cells so as to enhance their genomic stability and reverse the defects in the cellular phenotype observed. Dr. Lambert is course director of a widely subscribed course, Cellular Pathology, as well as the course DNA Repair in Health and Disease.

*Education
PhD, 1970 Northwestern University
B.A., 1966 Sweet Briar College, Sweet Briar, VA

Education

PHD, 1970, Northwestern University
B.A., 1966, Sweet Bliar College, Sweet Briar, VA

Relevant Publications

Gagna CE, Yodice AN, D'Amico J, Elkoulily L, Gill SM, DeOcampo FG, Rabbani M, Kaur J, Shah A, Ahmad Z, Lambert MW, Lambert WC. Novel B-DNA dermatophyte assay for demonstration of canonical DNA in dermatophytes: Histopathologic characterization by artificial intelligence. Clin Dermatol. Jan 6:S0738-081X(23)00270-5. 2024.

Lambert WC, Lambert MW, Sharquie K, Schwartz RA. Xeroderma pigmentosum: novel prophylactic and therapeutic approaches. Part III: Now more than just a therapeutic challenge. Skinmed 21(5):311-312, 2023

Shaarquie K, Jabbar RI, Schwartz RA, Lambert MW, Lambert WC. Xeroderma pigmentosum: Part two: Treatment of skin tumors with topical 25% podophyllin in benzoin. Skinmed 21(5):337-340, 2023.

Shaarquie K, Jabbar RI, Schwartz RA, Lambert MW, Lambert WC. Xeroderma pigmentosum: Novel prophylactic and therapeutic approaches. Part one: Topical zinc sulfate 25% and heat dermabrasion plus topical trichloroacetic acid. Skinmed 21(5):330-335, 2023

Lambert MW. The functional importance of lamins, actin, myosin, spectrin and the LINC complex in DNA repair. Exp Biol Med (Maywood). 44(15):1382-1406. 2019

Weiss A, Lambert MW, Lambert WC. Desquamative Dermatitis: A Dermatopathologic Emergency with Poorly Understood Etiopathogenesis. Skinmed. 2019;17(2):111-113. eCollection 2019. PubMed PMID: 31145062.

Metastectomy in Stage IV Melanoma: a National Cancer Database Analysis.Elias ML, Behbahani S, Maddukuri S, John AM, Schwartz RA, Lambert MW, Lambert WC. J Europ Acad Demratol Venereol. In press.

The Importance of Knowing Basic Biology in Making Critical Diagnoses: Off-label Dermatopathology. Karanfilian KM, Maddukuri S, Lambert MW, Elias ML, Behbahani S, Alhatem A, Lambert WC: SkinMed. In press.

The Physiology of Melanin Deposition in Health and Disease. Lambert MW, Maddukuri S, Karanfilian KM, Elias ML, Lambert WC. J Clin Dermatol, In press.

Areas Of Interest

DNA interstrand crosslinks

DNA repair

Fanconi anemia

Nonerythroid alpha spectrin

Telomeres and DNA repair

cancer predisposition diseases

genomic instability

Course List

PATH5100Q

Cellular Pathology

The research in my laboratory has focused on the role of DNA repair in genetic diseases with known DNA repair defects. These studies have concentrated on two genetic disorders, xeroderma pigmentosum and Fanconi anemia. Of particular interest have been investigations on the
underlying mechanism for the hematological disorder, Fanconi anemia (FA), which is characterized by bone marrow failure, aplastic anemia, diverse congenital abnormalities, genomic instability and a 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 its increased cleavage by ??-calpain and that this is an important factor in the DNA repair defect, telomere dysfunction and genomic instability observed in FA cells after ICL damage. 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 proteins to these sites and to the repair process. In FA cells, decreased levels of aIISp lead to reduced binding of aIISp to damaged DNA and to decreased levels of DNA repair. 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.