Melanoma is one of the most serious forms of skin cancer, but when found early, it’s highly treatable. Unfortunately, many people who are most at risk do not have easy access to dermatologists or affordable sun protection, making prevention and early detection more difficult. Our project focuses on patients seen at the DAWN Dermatology Clinic, a free, student-run clinic in Denver that serves uninsured Aurora residents. We are studying how our patients learn about skin cancer and melanoma prevention, including which social media or online sources they use and how much they trust that information. We are also testing how well artificial intelligence tools, such as ChatGPT, answer common patient questions about moles, sunscreen, and melanoma warning signs.

Our dermatology team reviews these artificial intelligence-generated answers using a standardized rubric developed by board-certified dermatologists to assess accuracy and safety. To help reduce UV exposure, we plan to give each participant SPF-protective shirts and sunscreen, items that many cannot afford but that make a real difference in melanoma prevention. These products are especially valuable for patients who work outdoors and spend long hours in the sun, which is common among our clinic population. By combining education, sun-protective resources, and evaluation of digital information quality, our project aims to close the melanoma prevention gap for underserved communities. We hope this effort will help patients recognize the early signs of melanoma, practice better sun safety, and feel empowered to protect their skin health.

Skin cancer is one of the most common and preventable types of cancer. Sun exposure and tanning increase the risk, but using sunscreen and avoiding sunburns can help prevent it. Some people, such as those who take medicines that weaken their immune system or who have certain medical conditions, are at higher risk for skin cancer. We do not know as much about whether these adults protect themselves from the sun as much as others. This project will use data from the 2024 National Health Interview Survey (NHIS), which asks thousands of adults across the United States about their health and sun-protection habits. The study will compare people who are immunosuppressed with those who are not to see how their sun behaviors and skin-cancer rates differ. The results will help identify who is less likely to practice sun safety and how doctors and public health programs can better teach and assist with sun protection strategies. This research will provide important information to guide future efforts to prevent melanoma and other skin cancers in people most at risk. 

Even after successfully removing a cutaneous melanoma (CM) primary tumor, the cancer can sometimes return years or decades later in other parts of the body; the main reason this cancer can be fatal. This recurrence happens because a few cancer cells escape the original tumor early on and travel elsewhere in the body, where they lie dormant, or “asleep,” for an extended period of time before suddenly “waking up” to form a new tumor. A critical mystery is what causes these cells to wake up when they do. Our research tackles this problem based on two key ideas. First, we believe only a subset of cells within the original tumor are primed to spread, lie dormant, and later wake up. Second, we can calculate how long these cells were dormant by reading the genetic changes accumulated in their DNA, like reading a molecular clock. In our preliminary work, we found that tumors with specific, recurring errors in genes that control cell growth were more likely to spread.

These errors, which make the cancer cells’ chromosomes unstable, seem to give them a special ability to travel and survive in the body. We have gathered a unique collection of tissue samples from 80 melanoma patients, each including their original tumor and the later metastasis. This direct comparison is essential to see what changed in the cells’ DNA during this dormant “asleep” period. Our first goal is to compare the primary and metastatic tumors to identify the exact “founder” cells that started the metastasis and understand what makes these founder cells different from the others. Our second goal is to use the DNA changes as a timer to calculate the dormancy period and pinpoint the specific genetic features that cause some cells to wake up quickly while others stay asleep for years. By understanding the mechanisms that keep these dangerous cells asleep and what triggers them to wake up, we hope to identify new treatment targets that can extend dormancy and prevent the cancer from returning. 

Acral lentiginous melanoma (ALM) is a rare kind of skin cancer that appears on the palms of the hands, soles of the feet, or under the nails, areas that may not be examined closely and can present with early signs that are hard to notice. As a result, ALM is often diagnosed at a later stage, when the cancer is thicker or has spread to nearby lymph nodes. This delay in diagnosis makes treatment more challenging and leads to worse outcomes compared to other types of melanoma. Past studies have suggested that ALM may be related to areas of repeated injury or slow wound healing. Many Veterans suffer from long-term nerve damage, known as peripheral neuropathy, or poor blood flow, called peripheral arterial disease (PAD).

These issues can lead to numbness, foot ulcers, and wounds that heal slowly, making the hands and feet more prone to ongoing injuries and poor healing that could lead to this melanoma. Despite this, researchers have not examined if peripheral neuropathy and PAD are directly related to the risk of developing ALM. To understand if they are, this study will look at data from 383 Veterans who have confirmed foot ALM and 383 similar Veterans who do not have it to examine if nerve damage or circulation issues raise the risk of developing ALM. We expect that Veterans with peripheral neuropathy and/or PAD will be more likely to develop foot ALM compared to those without these conditions. We will also investigate how these risks differ by age, sex, race, and ethnicity to identify groups that are at higher risk. By improving our understanding of whether nerve and blood vessel issues contribute to ALM, this research could help improve its screening and prevention efforts as well as possible therapeutic opportunities. 

Skin cancer is the most common cancer in the United States, and nearly one in five Americans will develop it during their lifetime. While most prevention efforts focus on sunscreen, clothing, and behavior changes, one important protective factor, access to shade, has received far less attention. Shade, created by trees and built structures, can reduce harmful ultraviolet (UV) radiation exposure. However, not all communities have equal access to shaded environments. Areas with fewer trees or less green space often overlap with communities that already face other health and environmental challenges. This project investigates whether communities with less shade experience higher rates of melanoma, the most serious form of skin cancer.

We are combining several national data sources, including the Centers for Disease Control and Prevention’s county-level cancer statistics, environmental shade data from the Tree Equity Score, UV exposure data from the National Institutes of Health, and demographic information from the U.S. Census. By analyzing these datasets together, we aim to understand how environmental and social factors interact to influence skin cancer risk. Early findings from New Jersey show that counties with less tree canopy coverage have higher rates of skin cancer. As our work expands nationally, we will identify which states and counties have the greatest need for shade-based interventions. The goal of this research is to establish shade availability as a key environmental factor in melanoma prevention and to provide evidence for policies that promote tree planting and shaded public spaces. By improving shade access, especially in communities with fewer resources, we hope to reduce future cases of melanoma and make skin cancer prevention more equitable and effective for everyone.  

Analysis of large families with more disease than expected has been shown to be a powerful way to identify cancer predisposition genes. We have used this approach in Utah to identify the major cancer genes BRCA1, BRCA2, as well as CDKN2A (identified in Utah and Texas cutaneous malignant melanoma (CMM) pedigrees). We have used the Utah high-risk pedigree approach more recently to identify genes for many cancers, including GOLM1 for CMM, as well as genes for other cancers (colon cancer, breast cancer, prostate and bladder cancer) and other disorders (e.g. Chiari malformations, osteoporosis, and Alzheimer’s). We propose to efficiently use this same approach here for an available resource of melanoma cases who died from their melanoma (lethal melanoma) and who belong to high-risk Utah melanoma pedigrees. In our Genetic Epidemiology Biorepository, we have 904 stored germline DNA samples from melanoma cases who are members of extended Utah pedigrees with a significant excess of melanoma (high-risk pedigrees). Among these sampled Utah cases there are 55 who have a linked Utah death certificate showing that melanoma was a contributing cause of death (lethal melanoma). Three of the pedigrees include 3 related affected sampled melanoma cases; the other 14 pedigrees include 2 related affected sampled melanoma cases.

We will perform whole genome sequencing (WGS) on these samples. We will apply a unique approach that includes analysis of the genetic sequence data to identify the rare genetic variants that are shared among these related Lethal melanoma cases; this will identify a set of strong candidate predisposition genes/variants for lethal melanoma. We will validate our candidates by testing for association with melanoma risk in publicly available data for independent populations of melanoma cases and controls (e.g. UKBiobank, VHA MVP, AllofUs). We will identify our top 10 candidate variants. We will assay the best candidates in the set of additional previously sampled and melanoma affected relatives of the affected cousin carriers (from our Biorepository) to confirm segregation in pedigrees. Identification of additional genes and variants responsible for lethal melanoma will improve identification of those people at most risk, will expand our understanding of the causes of lethal melanoma, and will allow the application of powerful screening and prevention strategies for this deadly cancer. 

Diabetes is chronic metabolic disorder of insulin resistance or deficiency. Diabetes has previously been linked to certain cancers: colorectal, liver, pancreatic, and endometrial; however, their association to melanoma remains unclear. Racial minorities make up about half of people with diabetes in the US and are more likely to have worse cancer outcomes. Additionally, racial minorities have worse melanoma outcomes in general. Given these prior findings, we aim to determine if there is a relationship between having diabetes and melanoma in racial minorities compared to Non-Hispanic White individuals. Our goal is to address a gap in knowledge in the literature while also contributing to future guidelines and recommendations for skin cancer screening.

Melanoma, a serious type of skin cancer, affects people differently based on their racial background. Non-Caucasian groups, such as Black, Asian, and Hispanic individuals, often face more barriers to early diagnosis and treatment, leading to worse outcomes. This research seeks to explore how genetic differences across racial groups might influence melanoma’s development, particularly focusing on common gene mutations known to drive this cancer. The study will analyze data from 470 melanoma cases in The Cancer Genome Atlas Program (TCGA) to see if specific gene mutations are linked to genetic differences in certain racial groups. The goal is to understand if certain populations are more likely to develop melanoma due to unique genetic factors. This analysis will look at mutations in key genes, like BRAF, NRAS, and NF1, which help melanoma grow and spread by activating pathways that increase cell survival and division. We will also explore how ultraviolet (UV) radiation and other factors contribute to melanoma’s high mutation rates. By identifying genetic patterns tied to specific racial groups, this study could pave the way for more personalized approaches to melanoma prevention and treatment, helping doctors provide better care for diverse populations and addressing existing health disparities.

This research explores the intricate relationship between proteins in the tumor environment, known as the extracellular matrix (ECM), and the behavior of natural killer (NK) cells, which play a crucial role in our immune defense against cancer. Specifically, we focus on melanoma, a type of skin cancer that is often characterized by high levels of collagen and diminished NK cell activity. Understanding how ECM components influence NK cell function could pave the way for innovative cancer therapies.
Our study has three main objectives. The first objective is to study the impact of collagen receptors on NK cells. A specific collagen receptor called LAIR 1 is known to limit the ability of NK cells to attack melanoma tumors. We will use mouse models to assess tumor growth and NK cell activity when LAIR 1 is absent to see if targeting LAIR 1 in the future can help NK cells attack melanoma tumors better. The second objective is to analyze the role of collagen III in NK cell activity. We aim to understand how collagen III alters NK cells to make them better in attacking melanoma cells. We will also specially designed mice without collage III to observe the changes that will occur in NK cells when they are exposed to melanoma cells. Our last objective is to discover the influence of other ECM proteins, such as elastin, on NK cell function. We will collect ECM from melanoma tumors and analyze its composition to investigate how these proteins affect NK cells in vitro.
Our findings could lead to innovative strategies and therapies for enhancing NK cell activity against solid tumors, specifically melanoma. It is promising that we may offer new avenues for cancer treatment and prevention. The projects could also be applied to other solid tumors, potentially improving outcomes for patients affected by various cancers.

Objectives: Our main goal is to understand how demographic factors influence the medical care patterns of individuals diagnosed with malignant melanoma. We also aim to see how these care patterns and demographics affect the chances of survival in these cases. Rationale: Research has highlighted the crucial role of factors like race and socioeconomic status in determining the severity and outcome of melanoma cases. Yet, we lack comprehensive data about how these factors impact the use of medical care before and after a new melanoma diagnosis, even though these factors are known to influence the disease’s impact. Methods: We are conducting a retrospective study using the Epic COSMOS database, containing records of over 220 million deidentified patients. We’re focusing on patients newly diagnosed with malignant melanoma of the skin. We’ll examine their interactions with healthcare providers six months, one year, two years, five years, and ten years before their diagnosis and categorize them based on their demographic characteristics. We’ll conduct similar analyses for healthcare visits to dermatologists, surgeons, and oncologists after diagnosis. Finally, we will try to understand how these patterns may affect mortality rates. Expected Results: We anticipate that patients with higher socioeconomic status, especially those who are white, will have more prediagnosis dermatology and preventive care visits, as well as more visits to dermatologists, surgeons, and oncologists after diagnosis. We also hypothesize that patients with fewer care visits both before and after diagnosis will face higher mortality rates.