Professor of Dermatology and Adjunct Professor of Oncological Sciences
Skin Cancer, Chemoprevention, p16
I was recruited to the Department of Dermatology and the Huntsman Cancer Institute in 2001. My research interests are focused on melanoma, the most serious form of skin cancer, which arises from melanocytes or nevi (moles). Our current work spans a spectrum from basic science (mechanisms of melanoma development and metastasis) to translational (melanoma chemoprevention) to clinical research (early melanoma detection). As a physician-scientist, I devote 75% of my effort to research and 25% of my effort to patient care (as Director of the Early Melanoma Detection clinic at HCI).
- Role of p16 and oxidative stress in melanoma. The CDKN2A (p16) gene is frequently mutated in families with melanoma predisposition, and suppressed by methylation or deleted in melanoma tumors. It is thought to function as a tumor suppressor by slowing the cell cycle and inducing senescence. We have reported an alternate function – regulation of oxidative stress, as its depletion from cells results in increased levels of reactive oxygen species without affecting the cell cycle. We recently showed that the increased ROS in cells lacking p16 results from an imbalance of increased mitochondrial biogenesis and impaired respiration. We are currently analyzing the effects of familial melanoma-associated mutations in p16 on these various activities.
- New agents for melanoma chemoprevention. We have previously worked with N-acetylcysteine (NAC) as an oral preventive agent for patients at risk for melanoma. We completed a phase II trial to test whether NAC can protect nevi from UV-induced oxidative damage which we have shown in a mouse model is important for melanoma development. Current research in this area is focused on aspirin, studying its metabolism in humans and mice, and its potential as a melanoma preventive agent using cellular, mouse, and human systems.
- Methods of early melanoma detection. We are using total body photography to monitor our patients who are at increased risk of melanoma, and have studied the role of photography in the physician decision to biopsy and early detection of melanoma. Current research in this area involves studying the survival outcomes of 3000 patients who have been monitored by photography over the past 14 years.
- Strunck JL, Smart TC, Boucher KM, Secrest AM, Grossman D (2020): Improved melanoma outcomes and survival in patients monitored by total body photography: A natural experiment. J Dermatol, 47: 342–347.
- Li C, Liu T, Tavtigian SV, Boucher K, Kohlmann W, Cannon-Albright L, Grossman D (2020): Targeted germline sequencing of patients with three or more primary melanomas reveals high rate of pathogenic variants. Melanoma Res, 30:247-251.
- Varedi A, Rahman H, Kumar D, Catrow JL, Cox JE, Liu T, Florell SR, Bucher KM, Okwundu N, Burnett WJ, Vanbrocklin MW, Grossman D (2020): ASA suppresses PGE2 in plasma and melanocytic nevi of human subjects at increased risk for melanoma. Pharmaceuticals, 13: https://doi.org/10.3390/ph13010007.
- Varedi A, Gardner LJ, Kim CC, Chu EY, Ming ME, Leachman SA, Curiel-Lewandrowski C, Swetter SM, Grossman D (2020): Use of new molecular tests for melanoma by pigmented lesion experts. J Amer Acad Dermatol, 82:245-247.
- Li C, Liu T, Liu B, Hernandez R, Facelli J, Grossman D (2019): A novel CDKN2A variant (p16L117P) in a patient with familial and multiple primary melanomas. Pigment Melanoma Cell Res, 32:734–738.
- Varedi A, Bishop MD, Kim CC, Boucher KM, Grossman D: (2019): Powering a prospective melanoma chemoprevention trial in high-risk cohorts. Int J Dermatol, 58:e232-234.
- Kumar D, Rahman H, Tyagi E, Liu T, Li C, Lu R, Lum D, Holmen SL, Maschek JA, Cox JE, VanBrocklin MW, and Grossman D (2018): Aspirin suppresses PGE2 and activates AMP kinase to inhibit melanoma cell motility, pigmentation and selective tumor growth in vivo. Cancer Prev Res (Phila), 11:629-642. (Featured on cover)
- Grossman D, Farnham J, Hyngstrom J, Klapperich ME, Secrest AM, Empey S, Bowen GM, Wada D, Andtbacka RHI, Grossmann K, Bowles TL, Cannon-Albright LA (2018): Similar survival of patients with multiple vs. single primary melanomas based on Utah SEER data (1973-2011). J Am Acad Dermatol, 79:238-244.
- Tyagi E, Liu B, Li C, Liu T, Rutter J, Grossman D (2017): Loss of p16INK4A stimulates aberrant mitochondrial biogenesis through a CDK4/Rb-independent pathway.Oncotarget, 8:55848-55862. (Priority Research Paper)
- Gardner LJ, Ward M, Andtbacka RHI, Boucher KM, Bowen GM, Bowles TL, Cohen AL, Grossmann K, Hitchcock YJ, Holmen SL, Hyngstrom J, Khong H, McMahon M, Monroe MM, Ross CB, Suneja G, Wada D, Grossman D (2017): Risk factors for development of melanoma brain metastasis and disease progression: a single-center retrospective analysis. Melanoma Res, 27:477-484.
- Cassidy P, Liu T, Florell SR, Honeggar M, Leachman SA, Boucher KM, Grossman D (2017): A phase II randomized placebo-controlled trial of oral N-acetylcysteine for protection of melanocytic nevi against UV-induced oxidative stress in vivo. Cancer Prev Res (Phila) 10:36–44.
- Truong A, Strazzulla L, March J, Boucher KM, Nelson KC, Kim CC, Grossman D (2016): Reduction in nevus biopsy rates in patients monitored by total body photography. J Am Acad Dermatol 75:135-143.