Luke H. Hoeppner, Ph.D.
Luke H. Hoeppner is an Assistant Professor and leader of the Cancer Biology research section at The Hormel Institute, University of Minnesota. As an undergraduate at the University of Wisconsin-Madison, Dr. Hoeppner identified several novel prostate cancer antigens, resulting in a first-author publication. He then received a Ph.D. from University of Minnesota studying cancer biology, which also provided him with a strong foundation in molecular, cellular, and biochemistry techniques. In his postdoctoral work, Dr. Hoeppner gained expertise working with genetic animal models. He developed a zebrafish VEGF-inducible model of vascular permeability amenable to non-invasive real-time fluorescent imaging as well as a human cancer metastasis xenograft model in zebrafish. Combining preclinical mouse cancer models and human translational studies, Luke developed an orthotopic lung cancer model and used it to demonstrate that FDA approved cabergoline and other dopamine D2 receptor agonists reduce lung tumor growth and angiogenesis. Along with other areas of current research, Dr. Hoeppner is investigating the contribution of downstream dopamine signaling effectors to drug resistance and lung cancer progression with the goal of developing new therapies.
- 2015 – Present:
- Assistant Professor
- University of Minnesota, The Hormel Institute, Austin, MN
- 2010 – 2015:
- Postdoctoral Fellow
- Mayo Clinic, Rochester, MN
- 2004 – 2010:
- Ph.D. in Cancer Biology
- University of Minnesota, Minneapolis, MN
- 2000 – 2004:
- B.S. in Genetics & Life Sciences Communication
- University of Wisconsin, Madison, WI
2016 – Present: Nature Partner Journals Precision Oncology -Editorial Board
University of Minnesota, Masonic Cancer Center
Mayo Clinic, Research Collaborator Adjunct Appointment
American Association for Cancer Research
International Association for the Study of Lung Cancer
Zebrafish Disease Models Society
American Heart Association
Our cancer biology research group studies the molecular mechanisms and signal transduction pathways that regulate vascular permeability, tumor angiogenesis, cancer drug resistance, and cancer initiation, progression and metastasis. We aim to translate our findings into new therapeutic strategies to cure patients suffering from cancer, cardiovascular disease, and stroke.
Understanding the role of dopamine signaling in lung cancer: A primary focus of our research is to understand the molecular basis of lung cancer, the leading cause of cancer-related death among Americans and worldwide. Specifically, we study the role of dopamine signaling in lung cancer. We demonstrated that dopamine D2 receptor (D2R) agonists abrogate non-small cell lung cancer (NSCLC) progression in syngeneic (LLC1) and human xenograft (A549) orthotopic murine models through inhibition of tumor angiogenesis and reduction of tumor infiltrating myeloid derived suppressor cells. Pathological examination of human NSCLC tissue revealed a positive correlation between endothelial D2R expression and tumor stage. NSCLC patients with a smoking history exhibited greater levels of D2R in lung endothelium. D2R agonists may represent a promising individualized therapy for NSCLC patients with high levels of endothelial D2R expression and a smoking history. Dopamine and cyclic-AMP-regulated phosphoprotein Mr 32000 (DARPP-32) is signaling molecule downstream of D2R. DARPP-32 and its truncated splice variant, t-DARPP, have been implicated in cancer cell proliferation, survival, invasion, metastasis, and angiogenesis. Our recent work is the first to show DARPP-32 isoforms promote lung tumor growth in orthotopic mouse models. We identified a novel physical interaction between DARPP-32 and inhibitory kappa B kinase-α (IKKα) that promotes NSCLC cell migration through non-canonical NF-κB2 signaling. Elevated t-DARPP isoform expression in NSCLC was found to be associated with poor overall survival and increasing tumor (T) stage, based on bioinformatics analysis of 513 lung adenocarcinoma patients. Correspondingly, immunohistochemistry showed that t-DARPP overexpression is correlated with increasing tumor (T) stage in 62 human lung adenocarcinoma tissues. Current studies further investigating the role of DARPP-32 isoforms in lung cancer will provide the foundation for new diagnostic and therapeutic approaches that will translate to significantly improved prognoses for cancer patients.
Development of in vivo models of vascular permeability and cancer metastasis: Another aspect of our research focuses on establishing genetic mouse and zebrafish models. Vascular endothelial growth factor (VEGF) induces vascular permeability (VP) in ischemic disease and cancer leading to many pathophysiological consequences. The molecular mechanisms by which VEGF acts to induce hyperpermeability are poorly understood and in vivo models that easily facilitate real-time, genetic studies of VP do not exist. We developed a heat-inducible VEGF transgenic zebrafish model through which VP can be monitored in real-time. Using this approach with morpholino-mediated protein knockdown, as well as mouse permeability models, we described a novel role of phospholipase Cβ3 (PLCβ3) as a negative regulator of VEGF-mediated VP by tightly regulating intracellular calcium release. We have also used this zebrafish model to elucidate the role of RhoC and other molecules in vascular homeostasis. The zebrafish vascular permeability model represents a straightforward method for identifying genetic regulators of VEGF-mediated VP as promising targets for cancer, heart disease and stroke therapies. We also developed a zebrafish xenograft model of human cancer cell metastasis, which was used in two separate studies to support our findings from murine cancer models. We are currently utilizing these in vivo models to better understand the molecular basis of VEGF-induced vascular permeability as well as cancer cell extravasation.
Reducing skin toxicity in cancer patients receiving radiation therapy: Radiation therapy is prescribed in over 50% of cancer patients because of its crucial role in improving local tumor control. Radiotherapy uses high energy X-rays to destroy cancer cells, but healthy skin tissue is collaterally damaged. Up to 95% of radiotherapy patients develop radiation-induced skin damage as a consequence of therapy. Acute radiation dermatitis represents a spectrum of adverse events, ranging from erythema to moist desquamation with ulceration. A current research goal is developing a topical molecular targeted therapy that mitigates radiation dermatitis to improve patients’ quality of life by improving comfort, avoiding treatment interruptions, and potentially permitting safe dose escalations.
2017 – 2019: “Paint the Town Pink” Pilot Project Award
2017 – 2018: University of Minnesota: Grant-in-Aid Shared Equipment Award
2014 – 2018: NIH Pathway to Independence Award (K99/R00)
2013 – 2014: American Heart Association Postdoctoral Fellowship
2010 – 2013: NIH Ruth L. Kirschstein National Research Service Award (T32)
- Alam SK, Astone M, Liu P, Hall SR, Coyle AM, Dankert EN, Hoffman DK, Zhang W, Kuang R, Roden AC, Mansfield AS, Hoeppner LH. DARPP-32 and t-DARPP promote non-small cell lung cancer growth through regulation of IKKα-dependent cell migration. Communications Biology. 2018;1. pii: 43. PMID: 29782621
- Ganaie AA, Beigh FH, Astone M, Ferrari MG, Maqbool R, Umbreen S, Parray AS, Siddique HR, Hussain T, Murugan P, Morrissey C, Koochekpour S, Deng Y, Konety BR, Hoeppner LH, Saleem M. BMI1Drives Metastasis of Prostate Cancer in Caucasian and African-American Men and Is A Potential Therapeutic Target: Hypothesis Tested in Race-specific Models. Clinical Cancer Research. 2018 [Epub ahead of print]. PMID: 30087142
- Astone M, Dankert EN, Alam SK, Hoeppner LH.Fishing for cures: The alLURE of using zebrafish to develop precision oncology therapies.Nature Partner Journals Precision Oncology. 1:39; 2017. PMID: 29376139
- Hoeppner LH, Wang Y, Sharma A, Javeed N, Van Keulen VP, Wang E, Yang P, Roden AC, Peikert T, Molina JR, Mukhopadhyay D. Dopamine D2 receptor agonists inhibit lung cancer progression by reducing angiogenesis and tumor infiltrating myeloid derived suppressor cells.Molecular Oncology. 9:270-81; 2015. PMID: 25226814
- Hoeppner LH, Sinha S, Wang Y, Bhattacharya R, Dutta S, Gong X, Bedell VM, Suresh S, Chun C, Ramchandran R, Ekker SC, Mukhopadhyay D.RhoC maintains vascular homeostasis by regulating VEGF-induced signaling in endothelial cells. Journal of Cell Science.2015. PMID: 26136364
- Cao Y, Hoeppner LH, Bach S, E G, Guo Y, Wang E, Wu J, Cowley MJ, Chang DK, Waddell N, Grimmond SM, Biankin AV, Daly RJ, Zhang X, Mukhopadhyay D. Neuropilin-2 promotes extravasation and metastasis by interacting with endothelial α5 integrin.Cancer Research.73(14):4579-4590; 2013. PMID: 23689123
- Hoeppner LH, Phoenix KN, Clark KJ, Bhattacharya R, Gong X, Sciuto TE, Vohra P, Suresh S, Bhattacharya S, Dvorak AM, Ekker SC, Dvorak HF, Claffey KP, Mukhopadhyay D. Revealing the role of phospholipase Cβ3 in the regulation of VEGF-induced vascular permeability.Blood.120(11):2167-73; 2012. PMID: 22674805
Complete publication list: https://www.ncbi.nlm.nih.gov/pubmed/?term=hoeppner+l
Primary Research Areas
- Cancer Biology
- Molecular Biology
- Vascular Function and Angiogenesis
- Lung cancer and drug resistance
- Cancer progression and tumor microenvironment
- Genetic mouse and zebrafish models
- VEGF-induced vascular permeability
- Radiation dermatitis