News
Celebrating the success of our trainees
It is always hard to say goodbye to trainees as they progress to the next phase of their careers, but we also enjoy their successes! Lots of good-bye lunches this summer! Patrick Juras moved to “The” Ohio State University where he started his residency in Internal Medicine. Debarati Mukherjee was recruited to Vividion Therapeutics (San Diego). Sandeep Artham joined The Jackson Laboratory in Sacramento. Madeline Newlin started her doctoral training in the Neurosciences program at Vanderbilt University.
New Lab Member
Dr. Vaishnavi Subramanyan has joined the laboratory as a post-doctoral fellow having recently obtained her PhD in Cancer and Stem Cell Biology from Duke-NUS medical school, Singapore. At Duke-NUS she worked under the mentorship of Dr. Patrick Casey to explore how the G-protein GNA13 impacts the pathobiology of ER+ breast cancers. In our laboratory she will be exploring the mechanisms by which prostate cancer cells recognize and respond differently to different levels on androgens; work that she hopes will direct mechanism-based discovery of new therapeutics for prostate cancer.
New Lab Member
Jillian Caiazzi is a first year pharmacology graduate student who has recently joined our laboratory to do her thesis research. Jillian is already an accomplished scientist with four years of experience working in the RNA Therapeutics Institute at UMass Chan Medical School. Specifically, she worked on the therapeutic development of siRNAs, focusing on extra-hepatic delivery and chemical optimization for specificity, potency, and duration of effect. With a bachelor’s degree in neuroscience, she is excited to be joining the McDonnell lab to pursue her passion of neuropharmacology and continue her training in an environment focused on translational research. Welcome Jillian!
Dr. McDonnell named a 2023 ASPET fellow
Donald McDonnell, PhD, has been named a 2023 ASPET Fellow (FASPET). The American Society for Pharmacology and Experimental Therapeutics(ASPET) bestows this prestigious honor on its most distinguished members.
View the 2023 FASPET Class announcement: https://www.youtube.com/watch?v=swz1lqnv
Congratulations, Dr. Dolan!
Emma (Dolan) successfully defended her doctoral thesis work presenting to a packed audience of family, friends, colleagues and professors. In an exceptional lecture she detailed how “Breast cancer cells recognize and respond to different levels of progestins to achieve different phenotypic outputs”. This is very impactful work which is instructive as to how progestins should be used clinically and how the progesterone receptor signaling pathways can be exploited in the development of new therapeutics (see doi: https://doi.org/10.1101/2023.10.13.562206). She was co-mentored during her graduate training study by Drs. Susan Murphy and Donald McDonnell. Emma is now doing postdoctoral research with Dr. Felix Feng (UCSF). Good Luck, Emma! (October 27, 2023)
Study published in Cancer Research validates CaMKK2 as a cancer cell intrinsic therapeutic target in cancer
Debarati Mukherjee led a study (recently published in Cancer Research) that defined a new CaMKK2-PDE1A-cGMP-PKG1-VASP signaling pathway involved in the regulation of the metastatic activity of triple-negative breast cancers and high-grade serous ovarian cancers [1]. This study validated CaMKK2 as a cancer cell intrinsic therapeutic target in cancer. However, previous work from the group also demonstrated that CaMKK2 inhibition in myeloid cells increased the cytotoxic activity of T cells and facilitated their recruitment to tumors (Nature Communications) [2]. Together these studies highlight the potential of CaMKK2 inhibitors as therapeutics which exhibit direct actions in cancer cells, but which also favorably remodel the tumor immune microenvironment. 1. Mukherjee, D., et al., Targeting CaMKK2 Inhibits Actin Cytoskeletal Assembly to Suppress Cancer Metastasis. Cancer Res, 2023. 83(17): p. 2889-2907. 2. Racioppi, L., et al., CaMKK2 in myeloid cells is a key regulator of the immune-suppressive microenvironment in breast cancer. Nat Commun, 2019. 10(1): p. 2450.
Lab Members Featured during PCB Retreat
The Department of Pharmacology and Cancer Biology recently held its annual retreat at Wrightsville Beach, NC. This retreat is an opportunity for trainees to present talks and posters and for the recently matriculated graduate students to see and hear the breadth of the science in the department. Our laboratory was well represented. Sandeep Artham (postdoctoral fellow) was selected to present a talk entitled “Estrogens suppress tumor associated tissue eosinophilia to promote tumor growth”. Trainees presented three posters: (1) “17 beta-estradiol negatively regulates natural killer cells and promotes breast cancer metastasis (Jovita Byemerwa, postdoctoral fellow), (2) “Breast cancer cells exhibit non-linear proliferative dose responses to progestins” (Emma Dolan, graduate student) and (3) “Targeting low dose androgen-mediated activation of mTOR signaling for the treatment of prostate cancer” (Min-yu Ko, graduate student). Each year at the retreat the recipients of the Fitzgerald Scholar awards are announced and presented to trainees who have published particularly impactful papers in their discipline within the past 12 months. Two members of the McDonnell laboratory were recipients of the 2023 Fitzgerald Awards. Debarati Mukherjee (postdoctoral Fellow) for her manuscript entitled “Targeting CaMKK2 Inhibits Actin Cytoskeletal Assembly to Suppress Cancer Metastasis” Cancer Res 2023 Sep 1;83(17):2889-2907 and Patrick Juras (postdoctoral fellow) for his paper “CaMKK2 Expression Is an Adaptive Response that Maintains the Fitness of Tumor-Infiltrating Natural Killer Cells” Cancer Immunology Res. 2023 Jan 3;11(1):109-122. (October 4, 2023)
McDonnell Discusses Statins and Cancer Prevention on HealthCall Radio Hour
In this interview, Donald Mcdonnell, PhD explains how statins are believed to prevent cancer. He explains that statins work by lowering cholesterol levels, which can help to reduce the risk of cancer. He also discusses the research that his lab has done on a specific type of cholesterol called 27-hydroxycholesterol, which he believes is a key driver of cancer growth.. (September 2, 2023)
Sermonix Pharmaceuticals Obtains Option to McDonnell Lab Technologies
Sermonix Pharmaceuticals, a biotech company focused on development and commercialization of oncology therapeutics for women, has obtained an option to several technologies out of the lab of Professor Donald McDonnell (Pharmacology and Cancer Biology, SOM). The technologies are a collection of small molecule regulators of tumor immunity, with an emphasis on improving the effects of immunotherapy against breast cancer. Sermonix had previously licensed another compound out of McDonnell’s lab (lasofoxifene) that is now in the clinic. (Summer 2023)
New Therapy for Advanced Breast Cancer has Roots in Duke Lab
On January 27, 2023, the Food and Drug Administration approved a new targeted therapy for hard-to-treat advanced breast cancers. Its development was made possible by research and advocacy from the lab of Donald McDonnell, PhD, Glaxo-Wellcome Distinguished Professor of Molecular Cancer Biology in the Department of Pharmacology and Cancer Biology.
The new drug, elacestrant, addresses a significant unmet need. It is the first and only treatment approved specifically to fight breast cancers with mutations in an estrogen receptor called ESR1, which make breast cancers resistant to standard endocrine therapy. (February 6, 2023)
Drug Discovered by Scientists in the McDonnell Laboratory Approved by the FDA for Use in Patients with Metastatic Breast Cancer
In 1996, while working in the laboratory of Donald McDonnell as graduate students, John Norris and Caroline Connor came up with the novel idea of developing drugs that induced such a dramatic conformational change in the estrogen receptor that the cell recognized it as denatured and disposed of it. They found that drugs that accomplished this activity were very effective inhibitors of the growth of breast tumors in animals.
They later discovered the first oral Selective Estrogen Receptor Degrader (SERD), Etacstil, and the drug was found to exhibit efficacy in patients with advanced breast cancer. Nearly 20 years later, Drs. Suzanne Wardell and Erik Nelson discovered a new SERD, Elacestrant, that was approved today by the FDA for use in the treatment of metastatic breast cancer. This is an amazing bench to bedside story and the culmination of 30 years work in the McDonnell laboratory. (January 27, 2023)
Irish Prime Minister Honors McDonnell with Science Medal
Taoiseach, Micheál Martin TD, has presented the prestigious Science Foundation Ireland (SFI) St Patrick’s Day Science Medal to Prof. Donald McDonnell, Associate Director for Translational Research for the Duke Cancer Institute and Glaxo-Wellcome Professor of Molecular Cancer Biology at Duke University School of Medicine in North Carolina, for his work in the development of new treatments for breast and prostate cancers. (March 17, 2022)
Link Between Melanoma and Estrogen Could Lead to New Therapeutic Approach
The link between estrogens and breast cancer has long been defined, but a Duke-led research team has identified how these hormones can also influence the growth of other cancers, notably melanoma. Building on observations that male melanoma patients who are treated with immune checkpoint inhibitors tend to have better responses than women, the team found that estrogens are a likely driver of the differences in outcomes. (October 12, 2021)
High Cholesterol Fuels Cancer By Fostering Resistance to a Form of Cell Death
Chronically high cholesterol levels are known to be associated with increased risks of breast cancer and worse outcomes in most cancers, but the link has not been fully understood. In a study appearing online Aug. 24 in the journal Nature Communications, a research team led by McDonnell lab members has identified the mechanisms at work, describing how breast cancer cells use cholesterol to develop tolerance to stress, making them impervious to death as they migrate from the original tumor site. (August 24, 2021)
A Bench-to-Bedside Story
“We’re always looking for stories where what we do at the bench impacts what we do in the clinic,” says Donald McDonnell, PhD, coleader of the Women’s Cancer Research Program at Duke Cancer Institute. “Like one where a young graduate student finds a drug, then the drug is patented, licensed, and in a phase two trial within a matter of a couple years. You can count on one hand the number of times that happens.” (January 7, 2021) This was one of those times.
The Drug Guy Changes Course
After a scientific meeting in New Hampshire in 2017, breast cancer researcher Donald McDonnell, PhD, met his wife, Mary, in Maine for a week of vacation. Sitting at a secluded inn on Anne’s Point, McDonnell, Coleader of the Women’s Cancer Research Program at the Duke Cancer Institute, couldn’t stop thinking about what he had heard at the meeting. He couldn’t shake the thought that he and everyone else had been taking the same general approach to treating estrogen-receptor-positive breast cancer for more than 30 years. (January 7, 2021)
McDonnell Elected to the National Academy of Inventors
Donald P. McDonnell, PhD, Glaxo-Wellcome Distinguished Professor of Molecular Cancer Biology in the School of Medicine, has been elected as a fellow to the National Academy of Inventors (NAI). The NAI recognizes academic inventors for their spirit of innovation in creating or facilitating outstanding inventions that have made a tangible impact on the quality of life, economic development and welfare of society. (December 14, 2020)
Brinker Award Recipient Dr. Donald McDonnell Says Research Advancements Are Bringing Us Closer to Cures for Breast Cancer
McDonnell, who is the Glaxo‐Wellcome Professor of Molecular Cancer Biology, Department of Pharmacology and Cancer Biology, Professor of Medicine, Co‐Director, Women’s Cancer Program, Duke Cancer Institute, Duke University School of Medicine, is this year’s recipient of the 2020 Susan G. Komen Brinker Award for Scientific Distinction in Basic Science. He is being recognized with Komen’s highest honor for the advancements he’s made in breast cancer research and medicine. He recently spoke with Susan G. Komen about his research. (December 8, 2020)
McDonnell Receives the 2020 Endocrine Society’s Gerald D. Aurbach Award for Outstanding Translational Research
This annual award recognizes outstanding contributions to research that accelerate the transition of scientific discoveries into clinical applications. As chair of the Department of Pharmacology & Cancer Biology within the Duke University School of Medicine in Durham, N.C., McDonnell has made major contributions to the biology and pharmacology of nuclear reception (NR) ligands. His work has been foundational for the development of a new generation of drugs for the treatment of hormone dependent cancers and metabolic disease.
New Approach to Shutting Down Breast Cancer Recurrence Shows Promise in Mice
A new approach to treat advanced breast cancer shuts down the growth of cells that become resistant to standard hormone therapy, according to McDonnell lab animal studies. The research, which is likely to be tested in clinical trials within the year, identified and targeted vulnerabilities that appear in nearly all estrogen-positive breast cancers that develop resistance to current treatments. (October 22, 2019)
Researchers Identify Enzyme That Suppresses Immune System in Breast Cancer
Immunotherapies have transformed cancer care, but their successes have been limited for reasons that are both complex and perplexing. In breast cancer especially, only a small number of patients are even eligible to undergo treatment with immunotherapies, and most see little benefit. But in a pre-clinical study led by the Duke Cancer Institute, researchers outlined a potential way to improve those results by uncloaking breast cancer tumors to the body’s immune system. (June 17, 2019)
Prostate Cancer Cells Grow with Malfunction of Cholesterol Control in Cells
Advanced prostate cancer and high blood cholesterol have long been known to be connected, but it has been a chicken-or-egg problem. Now a team led by researchers in the McDonnell lab have identified a cellular process that cancer cells hijack to hoard cholesterol and fuel their growth. Identifying this process could inform the development of better ways to control cholesterol accumulation in tumors, potentially leading to improved survival for prostate cancer patients. The findings are published online this month in the journal Cancer Research. (February 21, 2017)
McDonnell Elected to the National Academy of Medicine
Donald P. McDonnell, PhD from Duke University School of Medicine has been elected to the prestigious National Academy of Medicine, an independent advisory organization made up of leading professionals in health, medicine and the natural, social, and behavioral sciences. Dr. McDonnell was among 79 new members elected from both the United States and abroad. (October 20, 2016)
Cholesterol ‘Fuels’ Breast Cancer
A by-product of cholesterol can fuel the deadly growth and spread of breast cancer, according to a group of scientists. It raises the prospect that taking cholesterol-lowering drugs called statins could prevent cancer. The work, published in the journal Science, helps explain why obesity is a major risk factor for the disease. (November 29, 2013)
