Assistant Professor
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Research and Teaching Interests: Somatic Stem Cells and Aging, Genetic Mechanisms of Stem Cell Maintenance, Mouse Models of Hair Graying, Melanocyte Stem Cells

Melissa HarrisOffice Hours: By appointment

Education:
  • BS, University of California, Davis, Genetics (with a minor in English)
  • PhD, University of California, Davis, Cell and Developmental Biology
  • Postdoctoral/Research Fellow, National Human Genome Research Institute, NIH

For Dr. Melissa Harris, getting a gray hair is cause for celebration! This is because Dr. Harris studies the melanocyte stem cells that reside within our hair follicles, and it is the loss of these stem cells that causes gray hair. She has found that melanocyte stem cells are an ideal somatic stem cell population to investigate the cell biology, genetics, and genomics behind the question, “Why do we age the way we do?”

Research Opportunities

I am currently accepting Masters and PhD students into my lab. I am also recruiting for lab technician and undergraduate intern positions. If you are interested in joining my lab, please send me an email that outlines your research interests, as well as your curriculum vitae.
Dr. Harris’s training makes her well suited to this task; she’s studied pigmentation from the beginning while mixing in a combination of cell biology, developmental biology, genetics, and genomics along the way. Her interest in biological research as a career began in earnest as an undergraduate at the University of California, Davis. She interned in labs studying the population genetics of Dungeness crab, and applied genetic analysis to help uncover the genetic basis of coat color in horses. Dr. Harris performed her graduate work in the Department of Cell and Developmental Biology, also at UC Davis, where she studied with Dr. Carol Erickson. Here she used the chick embryo as a model to investigate the role of transmembrane receptors in directing the migration of melanoblasts, melanocyte precursors, into the skin. In 2009 she joined the National Human Genome Research Institute of the NIH and Dr. Bill Pavan’s lab as a postdoctoral fellow. Here she found footing in the world of biomedical research and established her current approach to exploit mouse models of hair graying to study mechanisms of somatic stem cell maintenance.

Throughout her time training, Dr. Harris has received numerous awards. She was recognized as a winner for the trans-institute, NIH Three-minute Talk competition where she was challenged to present her work in under three minutes in plain language. You can see her here, and be your own judge. Notably, she was also the recipient of an NIH Pathway to Independence Award from the National Institute on Aging, a five-year grant for postdocs transitioning to faculty positions. Beyond the lab, Dr. Harris has a genuine interest in teaching and mentoring and participated as a teacher in youth programs like 'Adventures in Science', as a mentor in undergraduate programs like the NIH Community College Summer Internship Program, and as a hands-on bioinformatics instructor within Honors College at the University of Maryland. In another realm, Dr. Harris is the mother of two rough-and-tumble kids who remind her daily that she only gets to be the boss when she’s in lab.

At UAB, Dr. Harris will use melanocyte stem cells and hair graying mouse models to address the role of genetic modifiers in stem cell-related aging phenotypes, cellular, and genetic mechanisms that lead to stem cell aging, and systemic factors that contribute to loss of stem cell maintenance. She hopes that her discoveries will garner insight into biomedical approaches to prevent and repair stem cell-related degenerative disease and improve the way we age.

Self-renewal of stem cells is essential to maintain long-term tissue homeostasis. One critical aspect of maintaining stem cell identity is the ability to suppress terminal differentiation; cues intended to promote differentiation in daughter cells must be adequately regulated in order to prevent differentiation in stem cells. Thus, over the lifetime of the organism, somatic stem cells need robust mechanisms to perpetuate this process in response to dynamic and variable regenerative requirements. And yet, a stem cell’s ability to manage differentiation programs changes with age. A clear understanding of the gene regulatory networks that impose on stem cell maintenance is an essential aspect of dissecting the aging phenotype.

In order to evaluate mechanisms for somatic stem cell self-renewal we have harnessed the melanocyte stem cell (McSC) and hair graying mouse models. Hair graying is a relevant, but understudied phenotype in regards to aging. In humans and mice, hair graying is associated with normal aging and is caused by premature McSC differentiation. Our previous studies of hair graying mouse models have shown that both the melanocyte lineage-specific differentiation program and unrelated, novel pathways can impact McSC maintenance. This suggests that the continued assessment of other hair graying mouse models may reveal additional genetic mechanisms regulating somatic stem self-renewal and differentiation. Using this approach and the tools we have established for interrogating McSCs (cellular, molecular, and genome-wide), we will investigate a number of hair graying mouse models. This is includes hair graying caused by exposure to ionizing radiation (and the role of reactive oxygen species in this process) and hair graying as a result of aging. We will identify the genetic factors associated with each hair graying model, elucidate their mechanisms, and then place them in the context of other genes in the McSC network and the aging stem cell network.

In addition to evaluating known hair graying mouse models, we are also identifying novel genetic pathways involved in McSC maintenance by identifying genetic modifiers of hair graying. Modifier genes have garnered increasing interest because of their potential contribution to variability in disease phenotypes. Longitudinal analyses of inbred mouse strains demonstrate that genetic background is also relevant to aging and lifespan. This suggests that identifying the genetic determinants responsible for variability in age-related phenotypes will yield novel insights into the cellular and molecular mechanisms for why we age the way we do. Using a genetic approach to predispose mice to premature McSC differentiation (Tg(Dct-Sox10)) we find that that the extent of McSC differentiation varies widely based on genetic background. Using genetic mapping approaches we can now identify the genetic basis of these strain-specific contributions to McSC maintenance. These studies underscore the relevance of evaluating genetic modifiers in age-related phenotypes, and suggest future investigations into whether these modifiers contribute more broadly to aging phenotypes in other tissues and whether this approach can predict predisposition for aging phenotypes in senile aging.
Adult hair pigmentation depends on the proper development of the melanocyte population as well as the maintenance of the melanocyte stem cells, a somatic stem cell population that resides in the hair follicle. During my postdoctoral studies, I found using the mouse model system that the regulation of lineage-specific transcription factors (e.g. Sox10) can serve two purposes within the postnatal melanocytes and melanocyte stem cells: support the survival of the adult melanocyte lineage, and determine melanocyte stem cell self-renewal and differentiation. Notably, my work contributed to our understanding of what drives melanocyte stem cell loss, namely, premature melanocyte stem cell differentiation. This observation supports the idea that various paradigms for stem cell loss exist. In respect to my current proposed research on stem cells and aging, this suggests that no one stem cell population fully models the mechanisms that affect stem cells as we age. Our recent ability to evaluate and compare cells on a genomic scale (as in Fufa, Harris, et al., 2015) may help identify common and unique gene regulatory networks associated with stem cells and the aging phenotype.

This work also elicited a useful publication on the characterization of a genetic tool for the conditional knockout of genes within the melanocyte stem cell population (Harris and Pavan, 2013).
  • Fufa TD, Harris ML, Watkins-Chow DE, Levy D, Gorkin DU, Gildea DE, Song L, Safi A, Crawford GE, Sviderskaya EV, Bennett DC, Mccallion AS, Loftus SK, Pavan WJ. Genomic analysis reveals distinct mechanisms and functional classes of SOX10-regulated genes in melanocytes. Hum Mol Genet. 2015 Oct 1;24(19):5433-50. PubMed PMID: 26206884; PubMed Central PMCID: PMC4572067.
  • Harris ML, Pavan WJ. Postnatal lineage mapping of follicular melanocytes with the Tyr::CreER(T) (2) transgene. Pigment Cell Melanoma Res. 2013 Mar;26(2):269-74. PubMed PMID: 23176440; PubMed Central PMCID: PMC4034131.
  • Harris ML, Buac K, Shakhova O, Hakami RM, Wegner M, Sommer L, Pavan WJ. A dual role for SOX10 in the maintenance of the postnatal melanocyte lineage and the differentiation of melanocyte stem cell progenitors. PLoS Genet. 2013;9(7):e1003644. PubMed PMID: 23935512; PubMed Central PMCID: PMC3723529.
  • Harris ML, Baxter LL, Loftus SK, Pavan WJ. Sox proteins in melanocyte development and melanoma. Pigment Cell Melanoma Res. 2010 Aug;23(4):496-513. PubMed PMID: 20444197; PubMed Central PMCID: PMC2906668.

The contribution of genetic background to variability in disease and aging is clear. However, identification of modifier genes that are relevant to aging and lifespan remains low. I have proposed that melanocyte stem cells can be useful in this regard. Disruption of this cell population leads to acute and measurable phenotypic outcomes that are essential to genetic mapping. In this publication I use this approach to demonstrate that loss of melanocyte stem cell differentiation (the phenotype associated with age-related hair graying) is variable amongst mouse strains of differing genetic background. This serves as the first step toward identifying the genetic modifiers that contribute to the variability of maintaining this stem cell population.
  • Harris ML, Levy DJ, Watkins-Chow DE, Pavan WJ. Ectopic differentiation of melanocyte stem cells is influenced by genetic background. Pigment Cell Melanoma Res. 2015 Mar;28(2):223-8. PubMed PMID: 25495036; PubMed Central PMCID: PMC4333083.
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