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 work has spanned the spectrum from basic science (mechanisms of melanoma development and metastasis) to translational (melanoma chemoprevention) to clinical research (early melanoma detection). More recent work has focused on clinical research and clinical trials. As a physician-scientist, I currently devote 65% of my effort to research and 35% of my effort to patient care (as Director of the Early Melanoma Detection clinic at HCI).
Recently Completed Projects
- 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 showed that the increased ROS in cells lacking p16 results from an imbalance of increased mitochondrial biogenesis and impaired respiration. We subsequently analyzed the effects of familial melanoma-associated mutations in p16 on these various activities.
- New agents for melanoma chemoprevention. We studied both N-acetylcysteine (NAC) and aspirin (ASA), an inhibitor of prostaglandin synthesis, as a potential UV-protective and prevention agent in mouse models and patients at increased risk for melanoma. While both agents conferred protection against some of the acute deleterious effects of UV radiation in mouse models, neither was able to prevent UV-induced DNA damage in human nevi in randomized phase II trials.
- Improved methods of early melanoma detection. We have been using total body photography to monitor our patients who are at increased risk of melanoma since 2004, and have studied the role of photography in the physician decision to biopsy and early detection of melanoma. We are currently testing novel non-invasive diagnostic techniques based on micro-RNA expression and artificial intelligence methods based on computer analysis of dermoscopic photographs for melanoma detection.
- Non-invasive detection of non-melanoma skin cancers. We are developing methods to diagnose basal and squamous cell carcinomas, and determine their depth of invasion using novel electrophysiologic and molecular techniques.
- Epidemiology of melanoma in Utah. Utah leads the nation in melanoma incidence, and from 1970-2010 melanoma-related mortality continues to rise in Utah while leveling off for the rest of the U.S. We are currently studying the factors related to melanoma recurrence and mortality in Utah as part of a collaborative effort with investigators at Intermountain Healthcare.
- Gene expression profiling (GEP) in melanoma. GEP testing of primary melanoma tumors can provide prognostic information, but is not currently advocated in national guidelines due to lack of demonstration of clinical utility. We are currently working to develop clinical trials to demonstrate whether GEP testing can be used to identify patients who could be spared the costs and toxicity of (or would benefit from) adjuvant therapy.
References (Selected Publications)
- Rahman H, Liu T, Askaryar S, Grossman D: Aspirin protects against UVB-induced DNA damage through activation of AMP kinase. J Invest Dermatol, in press.
- Okwundu N, Rahman H, Liu T, Florell SR, Boucher KM, Grossman D (2022): A randomized double-blind placebo-controlled trial of oral aspirin for protection of melanocytic nevi against UV-induced DNA damage. Cancer Prev Res 15:129-138.
- Luo X, Zhou Y, Smart T, Grossman D, Sanchez B (2022): Electrical characterization of basal cell carcinoma using a novel handheld electrical impedance dermography device. J Invest Dermatol Innovations 2:100075.
- Rahman H, Kumar D, Liu T, Okwundu N, Lum D, Florell SR, Burd CE, Boucher KM, VanBrocklin MW, Grossman D (2021): Aspirin protects melanocytes and keratinocytes against UVB-induced DNA damage in vivo. J Invest Dermatol, 141: 132-141.
- Grossman D, Sweeney C, Doherty JA (2021): Response to Welch et al “Rapid rise in incidence of cutaneous melanoma”. N Engl J Med, 384:e54.
- Grossman D, Okwundu N, Bartlett EK, Marchetti MA, Othus M, Coit DG, Hartman RI, Leachman SA, Berry EG, Korde L, Lee SJ, Bar-Eli M, Berwick M, Bowles T. Buchbinder EI, Burton EM, Chu EY, Curiel-Lewandrowski C, Curtis JA, Daud A, Deacon DC, Ferris LK, Gershenwald JE, Grossmann KF, Hu-Lieskovan S, Hyngstrom J, Jeter JM, Judson-Torres RL, Kendra KL, Kim CC, Kirkwood JM, Lawson DH, Leming PD, Long GV, Marghoob AA, Mehnert JM, Ming ME, Nelson KC, Polsky D, Scolyer RA, Smith EA, Sondak VK, Stark MS, Stein JA, Thompson JA, Thompson JF, Venna SS, Wei ML, Swetter SM (2020): Prognostic gene expression profiling in cutaneous melanoma: identifying the knowledge gaps and assessing the clinical benefit. JAMA Dermatol, 156(9):1004-1011.
- 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.
- 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.
- 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.