Notes on Dr. Melissa Harris — Hair, Stem Cells, Aging, and Gray Hair

Background and Journey

Dr. Melissa Harris is an associate professor in the Department of Biology and the director of the graduate research program. She emphasizes that she studies stem cells and aging, with a focus on a stem cell in hair that, when lost, leads to gray hair. She also notes the importance of mentoring and long-term career development for students.
Personal and career timeline:
- Born in Northern California in the mountains (the Lost Sierras) and grew up in a small town with a population similar to today.
- Undergraduate at the University of California, Davis, where she majored in genetics and discovered an interest in genetics research.
- Undergraduate internship at the UC Davis Veterinary Genetics Lab, which focused on identifying animals genetically for forensics and breeding. This lab worked heavily on horse coat color and genetic tests for poaching prevention.
- First-life lesson: showing up to interviews in the rain got her the internship when others didn’t show up; published her first two first-author papers during this period.
- Moonlighted in another lab on a population genetic study of Anter Magister (a crab species on the Northern California coast).
- Graduate work at UC Davis in the lab of Carol Erickson, studying embryonic pigment cell (melanocyte) migration in chick embryos to understand how pigment cells populate the skin.
- End of graduate school: had her first child, Finn (who is now 16). Two months after his birth, she moved to a postdoctoral position at the National Human Genome Research Institute (NHGRI) at NIH to align genetics and genomics with developmental biology.
- Postdoc at NHGRI/Gene Institute coincided with the tail end of the Human Genome Project, exposing her to cutting-edge genomic technologies (e.g., large-scale gene expression analyses) that she later brought to her lab at UAB.
- Second child, Penelope (14 now), and a reminder that a research career can coexist with family life.
- She emphasizes the importance of balancing life outside of work and that personal experiences (like losing her mother to breast cancer) inform her approach to research and career planning.
Purpose of her seminar is to introduce her scientific journey and then discuss gray hair biology and aging, with a focus on how stem cells in hair can inform aging and potential interventions.
Team hair us: a playful but informal name for her lab group, reflecting their focus on hair biology and their collaborative work.
Early professional shift toward aging and stem cells:
- Began with pigmentation genetics and embryology, but shifted to stem cell biology to address aging more broadly.
- Transitioned through several model systems to align questions with the most appropriate experimental context.

Research Focus and Lab Philosophy

Core research question: How do aging processes affect stem cell populations, and can we intervene to promote healthier aging by preserving or rejuvenating stem cell function?
Primary model system for her aging work: hair melanocyte stem cells within hair follicles.
Rationale for using hair melanocytes as a model:
- Hair growth involves a recurring activation of stem cells that generates pigment-producing melanocytes, which deposit pigment into growing hair.
- Plucking a hair can stimulate the stem cell pool to activate and regenerate a new hair, providing a simple, non-invasive experimental readout.
- Compared to muscle, hair follicle studies are less invasive: you can observe pigment changes externally rather than performing invasive tissue harvesting.
- The mouse hair follicle offers genetic tools and a mammalian system to study stem cell aging and potential rejuvenation.
Broader model-system versatility:
- Before hair, she studied pigmented cells in horses (coat color genetics) and pigment cell migration in chick embryos.
- These transitions illustrate that the choice of model depends on the specific biological question and how best to address it with available tools and readouts.
Cutting-edge technologies from NHGRI informed her: translational genomics approaches can illuminate stem cell aging in mammals and can be adapted for her head-lab work at UAB.

Model Systems and Methodological Flexibility

Horse coat color genetics:
- Genetic linkage studies to identify coat color genes and their chromosomal positions.
- Lessons learned about how phenotype relates to genotype in a practical, agricultural, and breeding context.
Chick embryo pigment cell migration:
- Early pigment cell (melanocyte) formation and migration from the neural crest into the skin.
- Chick embryos provide a convenient developmental window to manipulate and observe pigment cell dynamics.
- Demonstrated the concept that embryonic events set the stage for adult tissue color, which informs how stem cells contribute to tissue regeneration.
Mouse model for adult stem cells in hair:
- Allows investigation of melanocyte stem cell maintenance, dormancy, and activation across aging.
- Facilitates genetic tools to probe pathways (e.g., immune signaling) that influence stem cell populations.
High-throughput genomic and RNA sequencing tools:
- Learned at NHGRI and later incorporated into the UAB lab as technologies evolved beyond whole-genome RNA sequencing to newer, high-throughput approaches.
Work-life integration:
- She emphasizes that career progression can occur alongside family life, citing her children and her mother’s illness as part of a broader life narrative that informs career choices.

Hair Biology and Pigment: Anatomy and Mechanisms

Hair follicle architecture:
- Bulge region: the upper, bulge-like area where melanocyte stem cells are stored; responsible for replenishing pigment-producing cells.
- Bulb region: the lower part where pigment-producing melanocytes reside and deposit pigment into the growing hair via dendritic processes.
Pigment production and deposition:
- Melanocytes synthesize pigment and extend dendrites to deposit pigment into hair shafts during growth.
- Pigment presence in the hair shaft determines hair color; loss of pigment leads to gray/white hair.
Aging and pigment maintenance:
- With aging, the melanocyte stem cell pool can become depleted or dysfunctional, reducing pigment production and contributing to gray hair.
Stem cell activation in hair cycling:
- Each hair cycle involves activation of melanocyte and hair stem cells in response to hair shedding or injury signals.
- In younger individuals, melanocyte stem cells efficiently replenish pigment; in aging, this process deteriorates.
Heterochronic parabiosis as a conceptual example:
- An experimental setup pairing a young and an aged animal to share circulation; youthful systemic factors can promote rejuvenation of aged stem cell function, illustrating the potential for circulating cues to modulate aging tissues.
- This concept motivates the idea that aged stem cells may be receptive to rejuvenation cues if provided with the right signals.

Aging, Stem Cells, and Rejuvenation Concepts

Heterochronic parabiosis findings (conceptual):
- Young circulation can rejuvenate aged muscle stem cell function, suggesting aging phenotypes can be mitigated by circulating factors.
Implications for hair melanocyte stem cells:
- If similar rejuvenating cues exist for hair melanocyte stem cells, aging-related depigmentation might be reversible or preventable with the right signals.
Benefits of a non-invasive readout:
- Hair color changes provide an accessible, non-invasive phenotype to monitor stem cell function and aging-related decline.
Clinical and translational relevance:
- Understanding stem cell aging in hair could inform therapies for broader tissue aging and regenerative medicine strategies.

Gray Hair: Mechanisms, Evidence, and Implications

Classic mechanisms of graying:
- Disruption of pigment synthesis genes/proteins can cause gray hair (disruptive differentiation).
- Oxidative stress to melanocytes can cause DNA damage, mitochondrial mutations, and protein oxidation, contributing to graying.
- Melanocyte stem cell depletion or failure to maintain itself due to aging can lead to loss of pigment in hair follicles.
- Melanocyte stem cells may be lost or mis-differentiated (differentiating into other cell types or dying) resulting in reduced pigment production.
Stress and graying evidence:
- Capsaicin injections in mice can lead to local gray hair due to nerve release of noradrenaline, causing melanocyte stem cell migration away from hair follicles and impaired pigmentation.
- This provides a mechanistic link between stress and graying and offers a model for stress-induced pigment changes.
Real-world observations:
- The phenomenon of graying and potential reversion around high-stress periods (e.g., presidential terms) has been discussed in the literature and popular culture, aligning with mechanistic data on stress signaling affecting stem cells.
Reversibility questions:
- Graying can be reversible in some contexts, suggesting that residual melanocyte stem cells or dormant pools may be reactivated under certain conditions.

Gray Hair Reversal: Evidence from Human and Mouse Studies

Human observations and 2021 study:
- Regions of hair can be pigmented, then non-pigmented, and pigmented again within a single hair; this suggests that the same melanocytes can become active/inactive during different growth cycles.
- This “graying and reversion” implies melanocyte stem cells may be negatively affected by aging but retain potential for reactivation.
Market supplements and cautions:
- Not Today Gray product by Array suggested that nutritional supplementation could influence hair pigmentation, particularly in younger individuals with nutritional deficiencies.
- Ingredients discussed include vitamins, kava, black sesame seed extract, and Polygonum multiflorum (Foti Root), with claims of darkening hair in some contexts.
- Caution: high levels of vitamins/ supplements may have limited efficacy for age-related graying and may carry safety concerns given the presence of multiple bioactive compounds; patients should consult physicians before use.
Polygonum multiflorum (Foti Root) evidence:
- Polygonum extracts have been shown in literature to enhance pigmentation of melanocytes in various studies, supporting interest in whether such natural compounds can influence hair color.
- However, natural substances have diverse chemical components and potential negative effects; safety and standardization are critical considerations.
Immunotherapy observations and implications:
- In cancer patients treated with immunotherapies targeting the PD-1/PD-L1 axis, some individuals exhibited robust gray hair reversal, suggesting that immune-modulated signaling can influence melanocyte stem cell activity.
- The observation raises questions about whether PD-L1–related pathways help maintain stem cell dormancy; blocking PD-L1 could reactivate dormant stem cells and restore pigmentation.

PD-L1 Pathway and Immunotherapy: Hypotheses and Experimental Evidence

Core hypothesis:
- PD-L1-expressing melanocyte stem cells may be a dormant reservoir that can be reactivated when PD-L1 signaling is inhibited, potentially restoring pigment production in aging hair.
Human immunotherapy context:
- A clinical case series showed pronounced gray hair reversal in individuals treated with anti-PD-1/PD-L1 immunotherapies, suggesting a mechanistic link between immune checkpoint signaling and stem cell activity in pigmentation.
Mouse model validation:
- In mice, researchers created gray animals and administered anti-PD-L1; results showed reduced graying in treated groups, supporting the hypothesis that blocking PD-L1 can wake up dormant melanocyte stem cells.
Proposed mechanism:
- PD-L1 may help maintain melanocyte stem cell dormancy; when PD-L1 is blocked (e.g., by checkpoint inhibitors), stem cells are reinvigorated to produce pigment again.
Research program and intellectual property:
- The principal investigator discussed a provisional patent related to this concept, signaling an interest in translating the finding into practical applications.
Broader implications for other stem cells:
- The lab hypothesizes that PD-L1–related signaling may be a shared mechanism across different stem cell populations, including muscle stem cells, which could influence age-related muscle mass and function.
Experimental design in the lab:
- Mouse experiments include comparing young and aged mice; labeling and staining for PD-L1 to identify a potential dormant pool that can be reactivated by PD-L1 blockade.

Broader Implications: Beyond Hair to Tissue Aging

Potential cross-tissue relevance:
- If PD-L1–regulated dormancy is a general feature of stem cells, similar strategies might improve aging phenotypes in tissues such as muscle and brain.
- In muscle, aging is associated with sarcopenia; if muscle stem cells also express PD-L1, checkpoint blockade could influence muscle regeneration and mass.
Practical considerations:
- Immunotherapies carry risks and are designed for cancer treatment; applying these strategies to aging or cosmetic pigmentation would require careful safety and ethical considerations.
- Translational potential depends on identifying safe, targeted approaches that minimize adverse effects while delivering beneficial stem cell rejuvenation.
Additional hair biology observations:
- White hair fibers are typically thicker on average than pigmented hairs, suggesting different structural properties.
- White hairs may have different growth rates, potentially contributing to perceived density changes with aging.
Research directions:
- Exploring whether PD-L1–mediated dormancy is shared across hair and muscle stem cells could lead to broader aging interventions.
- Grants are in process to study immunotherapy-like approaches in aging-related contexts beyond pigmentation.

Practical, Ethical, and Life-Course Considerations

Work-life integration:
- The speaker emphasizes that a successful research career can coexist with family life, including having children during training and early career stages.
Family and mentoring:
- Personal experiences, such as the loss of her mother to breast cancer, inform her approach to mentoring and balancing obligations.
Intellectual property:
- A provisional patent was pursued on a concept integrating PD-L1 signaling and melanocyte stem cell activity, illustrating pathway from basic discovery to potential commercialization.
Community and student engagement:
- The lab and the broader center (Schoch Center) emphasize outreach, science communication, and public understanding of aging biology.

Team Harris: People, Mission, and Lab Culture

The team includes former and current members spanning past students and newer recruits, reflecting a collaborative, evolving research environment.
Mission and vision:
- To inspire and train the next generation of scientists through rigorous, collaborative biomedical research focused on hair biology as a gateway to understanding tissue aging.
- The long-term aim is to identify real biological solutions to combat tissue aging, starting with hair biology and extending to other tissues.
Lab culture and mentorship:
- Emphasizes collegiality, mentorship, and hands-on training for students to become proficient biomedical researchers.

Student Opportunities and Outreach Announcements

Biology Student Association (BSA):
- Faculty advisor role; a platform for undergraduates to engage with biology events, career opportunities, volunteering, and research experiences.
- Fundraising and outreach activities, including a turtle keychain sale at Stern Library to support turtle conservation; QR code provided for joining and leadership opportunities.
Nathan Schoch Center of Excellence in the Basic Biology of Aging:
- Center for advancing aging biology research and public awareness of long-term health.
- Looking for student interns focused on science communications related to aging biology.
- Intern responsibilities: manage social media, participate in myths vs. truths about aging, and promote science outreach as aging ambassadors.
How to get involved:
- Interested students should email the speaker directly about science communication internships and aging outreach opportunities.
Final note and Q&A:
- The talk concluded with open questions and a brief set of announcements from aging-related science organizations.

Key Terms, Concepts, and Takeaways

Melanocyte and melanocyte stem cell (MCSC): cells responsible for pigmentation; reside in the bulge region of the hair follicle; renewal leads to pigment deposition in hair.
Hair follicle anatomy: bulge (stem cell reservoir) and bulb (pigment deposition region).
PD-L1 (programmed death-ligand 1): immune checkpoint protein implicated in maintaining stem cell dormancy; blockade can awaken dormant stem cells and potentially restore pigmentation.
Immunotherapy context: anti-PD-1/PD-L1 therapies used in cancer can have pleiotropic effects, including hair color reversal in some cases.
Heterochronic parabiosis: experimental concept showing youthful factors can rejuvenate aged tissues via shared circulation, supporting the idea that aging phenotypes can be modulated by systemic signals.
Graying mechanisms: pigment synthesis gene disruption, oxidative stress, stem cell depletion, mis-differentiation, and stress-induced signaling (e.g., noradrenaline from nerves) affecting stem cell maintenance.
Graying reversal evidence: human hair growth studies showing reversible pigmentation within a single hair, and cancer immunotherapy case studies showing hair color restoration.
Natural supplements and pigmentation: Polygonum multiflorum (Foti Root) and other natural compounds can influence pigmentation in some studies; safety considerations are essential.
Musculoskeletal aging: potential shared PD-L1–related signaling in muscle stem cells, implying broader aging interventions beyond hair.
Ethical and practical considerations: balancing career with family life; IP and translation of basic science to clinical applications; safety and regulatory pathways for aging interventions.

Notable Dates and Numerical References (for quick recall)

Start at UAB and leadership in aging biology program (assistant/associate professorship): $02/2016$
Became the head of graduate research program and joined aging-focused biology nexus under former chair Steve Ostad: around $01/2020$
Her children: Finn (age ~16) and Penelope (age ~14) at the time of presentation; personal timeline emphasizes life events concurrent with a research career
The immunotherapy case series cited involved multiple subjects (e.g., roughly $13/14$ individuals showing reversal in a single study)
A 2021 study highlighted in the talk showed regional pigmentation changes within hair shafts, suggesting reversible pigmentation at the cellular level