Douglas Grossman

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 60% of my effort to research and 40% of my effort to patient care (as Director of the Early Melanoma Detection clinic at HCI).

Recently Completed Projects

1. 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.
2. 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.

Ongoing Projects

1. 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 in industry-sponsored trials.
2. 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. This work involves collaborations with Drs. Benjamin Sanchez-Terrones and Robert Judson-Torres. Some of this work is supported by multi-PI grants from NIH and the V Foundation.
3. 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.
4. 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.