Our laboratory is supported by grants from the National Institute of Neurological Diseases and Stroke, the National Multiple Sclerosis Society, and the European Leukodystrophy Association. These grants support research of proteins in the myelin sheath that are critical for normal human function. We study a protein, proteolipid protein, in myelin that is often mutated in humans and is fatal. Using molecular and cell biological techniques, we study the mechanisms by which mutations in this protein lead to cell death and, ultimately, a person's death. Inerestingly, we find that proteolipid protein is inserted into mitochondria where it exerts deleterious effects. We have available for study transgenic mice that mimic closely a human developmental disease. We also study sexual dimorphism of oligodendrocytes, the myelin forming cells in the central nervous system. Our laboratory is the first laboratory in the world to demonstrate morphological and functional differences in male and female oligodendrocytes.
More recently, our lab has been studying the role of proteolipid protein in neonatal hypoxia ischemia. We found that the absence of proteolipid protein is neuroprotective in hypoxia ischemia.
Our laboratory utilizes different molecular and cell biology techniques to study cell lineages and the regulation of myelin formation. These techniques include in situ hybridization, tissue culture, immunocytochemistry, cell transfections, myelin protein synthesis and targeting using enhanced green fluorescent protein as a marker protein, construction of point mutations in myelin protein genes, etc.
Research Educator, Full time, PhD, Gross Anatomy
Awards & Honors
- Wayne State University L.M. Weiner Distinguished Faculty Award, 2000
- Wayne State Univ. Distinguished Faculty Fellowship 1991-1993
- New York Academy of Sciences Certificate of Appreciation 1990
- Wayne State University Career Development Chair Award 1984
- NIH Study Sections 1982-present
- 1967, B.S., Spring Hill College, Mobile, AL (Biology)
- 1967-1971, Boston University, Boston, MA (Anatomy), Ph.D.
- 1971-1973, Washington University, St. Louis, MO.(Neurobiology), Postdoctoral Fellow, Director: Dr. Viktor Hamburger.
- Instructor: (Neurology), Johns Hopkins Univ. School of Medicine; 1973-1974
- Assistant Professor: (Neurology), Johns Hopkins Univ. School of Medicine;1974-1978.(Anatomy), Johns Hopkins Univ. School of Medicine;1976-1978.
- Associate Professor: (Anatomy), Wayne State Univ. School of Medicine;1978-1985.(Tenure granted 1980)
- Professor: (Anatomy), Wayne State Univ. School of Medicine; 1985- present
- Neurology (Adjunct), Wayne State Univ. Sch. of Med.; 1988- present
- Center for Molecular Medicine and Genetics (Adjunct), Wayne State Univ. Sch. of Med.; 1998-present
- Novel pathologic findings in patients with Pelizaeus-Merzbacher disease. Laukka JJ, Kamholz J, Bessert D, Skoff RP. Neurosci Lett. 2016 Aug 3;627:222-32. doi: 10.1016/j.neulet.2016.05.028. Epub 2016 May 17. PMID: 27222925
- Insertion of proteolipid protein into oligodendrocyte mitochondria regulates extracellular pH and adenosine triphosphate.Appikatla S, Bessert D, Lee I, Hüttemann M, Mullins C, Somayajulu-Nitu M, Yao F, Skoff RP. Glia. 2014 Mar;62(3):356-73. doi: 10.1002/glia.22591. Epub 2013 Dec 31. PMID: 24382809
- Gait abnormalities and progressive myelin degeneration in a new murine model of Pelizaeus-Merzbacher disease with tandem genomic duplication. Clark K, Sakowski L, Sperle K, Banser L, Landel CP, Bessert DA, Skoff RP, Hobson GM. J Neurosci. 2013 Jul 17;33(29):11788-99. doi: 10.1523/JNEUROSCI.1336-13.2013. PMID: 23864668
- Boucher SEM, Carlock LR, Skoff RP. Proteolipid protein gene modulates viability and phenotype of neurons. J. Neurosci. 22:1772-1783 (2002). Medline Determinants of central nervous system adult neurogenesis are sex, hormones, mouse strain, age, and brain region. Tatar C, Bessert D, Tse H, Skoff RP. Glia. 2013 Feb;61(2):192-209. doi: 10.1002/glia.22426. Epub 2012 Oct 1.PMID: 23027402
- Skoff RP, Bessert DA, Cerghet M, Rout UK, Nave K-A, Carlock L, Ghandour MS, Armant DR. The myelin proteolipid protein1 gene modulates apoptosis in non-neural tissues. Cell Death and Differentiation, 11:1247-1257 (2004). Medline
- Cerghet M, Skoff RP, Bessert D, Zhang Z, Mullins C, Ghandour MS. Proliferation and death of oligodendrocytes and levels of myelin proteins are differentially regulated in male and female rodents. J. Neurosci. 26:1439-1447 (2006). Medline
- Huttemann M, Zhang Z, Mullins C, Bessert D, Lee I, Nave KA, Appikatla S, Skoff RP. Different proteolipid protein mutants exhibit unique metabolic defects. ASN Neuro. 1. pii : e00014 (2009).
- Sima AA, Pierson CR, Woltjer RL, Hobson GM, Golden JA, Kupsky WJ, Schauer GM, Bird TD, Skoff RP, Garbern JY. Neuronal loss in Pelizaeus-Merzbacher disease differs in various mutations of the proteolipid protein 1. Acta Neruopathol. (2009).
- Swamydas M, Bessert D, Skoff R. Sexual dimorphism of oligodendrocytes is mediated by differential regulation of signaling pathways. J. Neurosci. Res. (2009).