Kristy Brown, Ph.D.

Kristy A. Brown, Ph.D., earned her doctorate in reproduction from the Université de Montréal (Canada) in 2006. She then joined Prince Henry’s Institute (Australia) as an FQRNT Postdoctoral Fellow (2006-2008) and later became a Terry Fox Foundation Fellow through the National Cancer Institute of Canada (2008-2011). Following the receipt of an NHMRC Career Development Award and an NHMRC project grant, she was appointed co-Head of the Metabolism and Cancer Laboratory at Prince Henry’s Institute. She transitioned to the position of Research Group Head at the Hudson Institute for Medical Research in 2014, where she received the Mavis Robertson Award from the National Breast Cancer Foundation. In 2017, she was recruited to the Department of Medicine at Weill Cornell Medicine (USA) and in 2020 was promoted to Associate Professor of Biochemistry in Medicine. In 2022, she was awarded the Emilie Lippmann and Janice Jacobs McCarthy Research Scholar Award in Breast Cancer. Dr. Brown was recruited in 2023 to the University of Kansas Medical Center as Associate Professor of Metabolism and Cancer and Co-Program Leader for the Cancer Prevention and Control Program of the KU Cancer Center. Additionally, she is a member of the KU Diabetes Institute and serves as the Director of Workforce Equity for the Kansas Center for Metabolism and Obesity Research (KC-MORE) COBRE. She has published 81 peer-reviewed articles and two books. She also holds two patents and has been an invited speaker at more than 90 conferences and events, as well as numerous public outreach efforts. She is ranked among the top 0.007% of published authors for ‘aromatase’, 0.11% for ‘obesity’, and 0.13% for ‘breast cancer’ (Expertscape).

Obesity is a leading modifiable risk factor for at least 13 types of cancer, including hormone receptor-positive breast cancer after menopause. Several local and systemic changes are hypothesized to support this relationship, including increased circulating levels of insulin and glucose, as well as adipose tissue-derived estrogens, adipokines and inflammatory mediators. Metabolic pathways of energy production and utilization are dysregulated in tumor cells and this dysregulation is a newly accepted hallmark of cancer. Dr Brown's team has driven groundbreaking work to understand the role of metabolic pathways in the breast microenvironment and in regulating aromatase, the enzyme responsible for the production of estrogens, in driving breast cancer risk in obesity. Based on these discoveries, they identified the AMPK-activating anti-diabetic drug metformin as a tissue selective inhibitor of estrogen production.

Through these studies, an appetite-regulating hormone was identified as a potential new breast cancer therapeutic. Ghrelin and its unacylated form, des-acyl ghrelin, are produced predominantly by the gut and circulating levels are inversely associated with obesity. They found that ghrelin and des-acyl ghrelin potently inhibit aromatase and estrogen production in breast adipose tissue, not only providing an additional mechanism for the obesity-associated increase in aromatase, but also leading to the hypothesis that des-acyl ghrelin analogues may be of therapeutic relevance. The team's work has also explored the effects of des-acyl ghrelin on tumor growth. Effects appear to be tumor-type specific and dependent on interaction with the extracellular matrix.

Following on from this work, the impact of obesity and breast adipose-derived factors on breast tumorigenesis was explored. The lab was particularly interested in understanding whether poor metabolic health may contribute to breast cancer penetrance in BRCA mutation carriers. These women have an elevated risk of developing breast and ovarian cancer, yet little is known as to whether modifiable risk factors contribute to tumor formation. In NIH-funded work, body mass index (BMI) and markers of metabolic dysfunction were found to be positively correlated with more DNA damage in the non-cancerous breast epithelium of BRCA mutation carriers. Data in high fat diet-fed Brca1-/+ mice support a role for obesity in driving DNA damage in the normal mammary gland. Mechanistic studies have demonstrated that the estrogen receptor degrader fulvestrant or anti-diabetic drug metformin can reduce DNA damage in human tissue, suggesting potential opportunities for intervention. Using a carcinogen-induced Brca1 -/+ model developed in the Brown lab, high fat feeding was found to lead to increased tumor penetrance.

Breast adipose tissue-derived extracellular vesicles from obese women alter tumor cell metabolism.

Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers

Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers.

Ghrelin and des-acyl ghrelin inhibit aromatase expression and activity in human adipose stromal cells: suppression of cAMP as a possible mechanism.

Hyperglycemia in acute COVID-19 is characterized by insulin resistance and adipose tissue infectivity by SARS-CoV-2

Inhibition of EZH2 Catalytic Activity Selectively Targets a Metastatic Subpopulation in Triple-Negative Breast Cancer

Leptin regulation of the p53-HIF1α/PKM2-aromatase axis in breast adipose stromal cells: a novel mechanism for the obesity-breast cancer link.

Metabolic pathways in obesity-related breast cancer

Metabolic pathways in obesity-related breast cancer.

Obesity promotes breast epithelium DNA damage in women carrying a germline mutation in BRCA1 or BRCA2

Obesity promotes breast epithelium DNA damage in women carrying a germline mutation in BRCA1 or BRCA2.

PPARγ antagonists induce aromatase transcription in adipose tissue cultures.

Prostaglandin E2 inhibits p53 in human breast adipose stromal cells: a novel mechanism for the regulation of aromatase in obesity and breast cancer.

Three-dimensional growth of breast cancer cells potentiates the anti-tumor effects of unacylated ghrelin and AZP-531

Three-dimensional growth of breast cancer cells potentiates the anti-tumor effects of unacylated ghrelin and AZP-531.

Update on Adipose Tissue and Cancer

Update on Adipose Tissue and Cancer.

Characterizing the autologous fat graft microenvironment resulting from differential intraoperative processing techniques: A comparative analysis and its clinical implications

Digital Lifestyle Intervention to Improve Normal Weight Obesity in Primary Breast Cancer

Effects of Tirzepatide on Blood, Imaging and Breast Tissue Biomarkers in Women with Obesity and Other Risk Factors for Breast Cancer: A Feasibility Study

Identifying metabolic vulnerabilities of breast epithelium in BRCA1 mutation carriers with obesity and impact of exercise and anti-obesity medications for cancer prevention: a focus on mitochondrial function and DNA damage

In-vivo Characterization of White Adipose Tissue with Quantitative Ultrasound

Kansas Center for Metabolism and Obesity Research (KC-MORE) Center of Biomedical Research Excellence Women’s Health Supplement