Marc Vermulst, Ph.D.
- Assistant Professor, Department of Pathology and Laboratory Medicine
Colket Translational Research Building, Room 6014
3501 Civic Center Boulevard
The primary goal of my lab is to understand the mechanistic basis of the aging process. Understanding human aging is perhaps the most important goal of modern medicine today, since most diseases that are currently endemic in Western society are age related diseases. Thus, if we had a deeper appreciation for the aging process itself, we would be in a better position to treat, or prevent various diseases, such as cancer, heart failure and neuronal degeneration.
This rationale shapes the research we do in our lab and ensures that our experiments are always at the crossroads of basic biology and medical urgency.
Proteotoxic stress: Many age-related diseases, including Alzheimer’s disease and Parkinson’s disease, are caused by proteotoxic stress. When examined, the neuronal networks of these patients are crowded with protein aggregations that impair cognitive function. To delay the progression of these diseases, and ultimately to prevent them, it will be important to understand how protein aggregation is initiated. We have found a link between DNA transcription and proteotoxic stress that helps explain the etiology of these diseases.
Stem cell biology: Stem cells are the most important residents of our tissues. They replenish cells that are lost over time, and give rise to specialized groups of cells that are required for tissue homeostasis. Accordingly, age-related changes in stem cell behavior may contribute to the decline in tissue function seen with old age. To investigate this possibility, we are studying stem cell dynamics as a function of age.
Mitochondrial DNA dynamics: Mitochondria are the powerhouses of the cell. They supply our cells with energy and mediate numerous processes that are essential to human health. As we grow older, mitochondria decline in function, and this can have a negative effect on cells with a high metabolic load, especially muscle fibers and neurons. Although the mechanisms behind this age-related decline are unclear, it is thought that mitochondrial DNA is a central component of this problem. Our goal is to unravel mtDNA genetics at a subcellular level to understand why mitochondrial function declines in aging muscle cells and neurons.
Carcinogenesis: Cancer is one of the most common age-related diseases in humans. To successfully treat cancer, it will be important to identify the Achilles’ heel of tumor progression. A deeper understanding of the cellular dynamics that drive tumor growth could contribute to this effort. Our goal is to unravel the complex cellular dynamics inside a growing tumor mass to expose new targets for treatment.
Post-doctoral positions are available
Vermulst M, Bielas JH, Kujoth GC, Ladiges WG, Rabinovitch PS, Prolla TA and Loeb LA. (2007) Mitochondrial point mutations do not limit the natural lifespan of mice. Nat Genet. 39, 540‐543
Associated Commentary: Mitochondrial DNA mutations and aging: a case closed? Konstantin Khrapko and Jan Vijg, Nat Genet. 2007 39: 445‐446
Vermulst M, Wanagat J, Kujoth GC, Bielas JH, Rabinovitch PS, Prolla TA and Loeb LA. (2008) DNA deletions and clonal muttions drive premature aging in mitochondrial mutator mice. Nat Genet. 40, 392‐4
Vermulst M, Bielas, JH, Loeb, LA. (2008) Quantification of mutation in the mitochondrial genome (2008) Methods. Dec;46(4):263‐8.
Dai D, Santana LF, Vermulst M, Tomazeva DM, Emond MJ, Macoss MJ, Gollahon K, Martin GM, Loeb LAL, Ladiges, Loeb LA, Rabinovitch PS (2009). Overexpression of catalase targeted to mitochondria attenuates murine cardiac aging, Circulation, 2009 Jun 2;119(21):2789‐97.
HC Chen*, Vermulst M*, Wang YE, Prolla TA, McCaffery MJ, Chan DC. Mitochondrial fusion is required for mtDNA stability and tolerance of mtDNA mutations. Cell, 2010, April 16; 141(2): 280‐9. *equal contributors
N Ericson, M Kulawiec, M Vermulst, K Sheahan, J O'Sullivan, J J Salk, Jason H. Bielas. Decreased Mitochondrial DNA Mutagenesis in Human Colorectal Cancer. PLoS Genet. 2012;8(6): e1002689. doi: 10.1371/journal.pgen.1002689. Epub 2012 Jun 7