Luke Hoeppner, PhD

Luke Hoeppner

The Hormel Institute
801 16th Avenue NE
Austin, MN 55912
United States

Assistant Professor, The Hormel Institute 


Assistant Professor, The Hormel Institute, Masonic Cancer Center (MCC)

PhD, University of Minnesota (Cancer Biology), 2010

BSc, University of Wisconsin (Genetics), 2004

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Research Summary/Interests

Dr. Hoeppner is an investigator at The Hormel Institute. His primary research focus is discovering new ways to combat lung cancer using molecular, genetic, and biochemical approaches. The main goal is to rapidly identify prognostic indicators, therapeutic targets, and strategies to overcome drug resistance in lung cancer patients. Dr. Hoeppner’s laboratory also studies molecular mechanisms and signal transduction pathways involved in vascular permeability, angiogenesis, cancer progression, metastasis, and adverse effects of cancer therapy. Specific research directions are described below.


1. Triggering the dopamine pathway to inhibit non-small cell lung cancer progression: Lung cancer is the leading cause of cancer-related death worldwide. We demonstrate that elevated expression of dopamine and cyclic adenosine monophosphate-regulated phosphoprotein, Mr 32000 (DARPP-32) and its truncated splice variant t-DARPP promote lung tumor growth, while abrogation of DARPP-32 expression in human non-small cell lung cancer (NSCLC) cells reduces tumor growth in orthotopic in vivo models. We observe a novel physical interaction between DARPP-32 and inhibitory kappa B kinase-? (IKK?) that promotes NSCLC cell migration through non-canonical nuclear factor kappa-light-chain-enhancer of activated B cells 2 (NF-?B2) signaling. Bioinformatics analysis of 513 lung adenocarcinoma patients reveals elevated t-DARPP isoform expression is associated with poor overall survival. Histopathological investigation of 62 human lung adenocarcinoma tissues also shows that t-DARPP expression is elevated with increasing tumor (T) stage. Our data suggest that DARPP-32 isoforms serve as a negative prognostic marker associated with increasing stages of NSCLC and may represent a novel therapeutic target. We are now beginning to investigate the role of DARPP-32 isoforms in different subtypes of lung cancer, specifically EGFR mutant NSCLC and small cell lung cancer. A current area of focus is to understand how DARPP-32 and t-DARPP promote resistance to molecular targeted therapies.

2. DARPP-32 drives small cell lung cancer growth and neuroendocrine tumor cell survival: Small cell lung cancer (SCLC) is the most aggressive form of lung cancer, and new molecular insights are necessary for prognostic and therapeutic advances. We demonstrate in orthotopic models that DARPP-32 and its splice variant t-DARPP promote SCLC growth through increased proliferation, Akt/Erk-mediated survival and anti-apoptotic signaling. DARPP-32 and t-DARPP proteins are overexpressed in SCLC patient-derived tumor tissue, but virtually undetectable in physiologically normal lung. RNA sequencing analysis reveals a subset of SCLC patients with high tumoral t-DARPP expression and upregulated Notch signaling genes, including achaete-scute homologue 1 (ASCL1). We show that DARPP-32 isoforms are transcriptionally activated by ASCL1 in human SCLC cells. Taken together, we demonstrate new regulatory mechanisms of SCLC oncogenesis that suggest DARPP-32 isoforms may represent a negative prognostic indicator for SCLC and serve as a potential target for the development of new therapies.


3. VEGF activates STAT3 to promote vascular permeability: Vascular endothelial growth factor (VEGF) induces vascular permeability in ischemic diseases and cancer, leading to many pathophysiological consequences. For example, in heart attack or stroke, expression of VEGF leads to vascular permeability, edema, and tissue damage. However, following cardiovascular or cerebrovascular infarct, VEGF promotes repair of ischemic tissue. Consequently, understanding the molecular mechanisms of VEGF-induced vascular permeability will facilitate the development of promising therapies that achieve the delicate balance of inhibiting vascular permeability while preserving ischemic tissue repair mediated by VEGF signaling. VEGF signals through its receptor, VEGFR-2, to activate signal transducer and activator of transcription 3 (STAT3). Phosphorylation of STAT3 promotes its nuclear translocation, enabling STAT3 to transcriptionally activate target genes. We show in human umbilical vein endothelial cells (HUVEC) that VEGF induces VEGFR-2/STAT3 association, STAT3 phosphorylation, and STAT3 nuclear localization. We demonstrate that STAT3 positively regulates VEGF-mediated vascular permeability by utilizing a VEGF-inducible zebrafish model in conjugation with STAT3 knockout zebrafish generated using CRISPR-Cas9 genome editing. We also confirm STAT3 promotes VEGF-induced vascular permeability in a mammalian model system. Taken together, our results suggest STAT3 plays a critical role in VEGF-induced vascular permeability, which may translate to improved therapies for patients afflicted by heart disease, stroke, or cancer.


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 lung cancer growth through IKK?-dependent cell migration. Communications Biology. 1:43; 2018. PMID: 29782621

Alam SK, Wang L, Ren Y, Hernandez CE, Kosari F, Roden AC, Yang R, Hoeppner LH. ASCL1-regulated DARPP-32 and t-DARPP stimulate small cell lung cancer growth and neuroendocrine tumor cell survival. BioRxiv. 2019.

Ganaie A, 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. BMI1 drives 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. 24:6421-6432; 2018. PMID: 30087142

Wang TY, Wang L, Alam SK, Hoeppner LH, Yang R. ScanNeo: identifying indel derived neoantigens using RNA-Seq data. Bioinformatics. 35:4159-4161; 2019. PMID: 30887025

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. 128:3556-68; 2015. PMID: 26136364

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 C?3 in the regulation of VEGF-induced vascular permeability.Blood. 120(11):2167-73; 2012. PMID: 22674805