Dr. Luke Hoeppner and his group study the molecular events that drive lung cancer initiation, progression, metastasis, and resistance to therapy with the goal of discovering new ways to treat cancer. We also investigate how damaged blood vessels can be repaired to treat a variety of human diseases, including cardiovascular disease, lung injury, cancer, and metastasis. 

Our research focuses on establishing mouse and zebrafish models of human disease. We are currently using these in vivo models to better understand the molecular basis of vascular permeability as well as cancer cell extravasation. As an example of the former pursuit, we have shown that suppressing STAT3 activity protects the endothelial barrier from VEGF-mediated vascular permeability (Disease Models & Mechanisms, 2021) using mouse models and heat-inducible VEGF zebrafish we genetically developed (Blood, 2012).

The Hoeppner Lab is dedicated to developing new approaches to prevent the progression of therapy-resistant lung cancer. Small cell lung cancer (SCLC) is among the most lethal forms of lung cancer. SCLC is an aggressive disease that metastasizes to other organs early compared to other cancers and rapidly acquires resistance to chemotherapy, making it exceptionally challenging to treat. We recently discovered that activating the dopamine D₂ receptor (D₂R) with a specific agonist can suppress the growth of new tumor blood vessels (angiogenesis), thereby slowing cancer progression. In our recent study, published in Cell Death & Disease (2025), we used cabergoline, an FDA-approved D₂R agonist, to reduce angiogenesis and overcome chemotherapy resistance in models of SCLC, enhancing the effectiveness of other treatments. Activation of dopamine signaling reduces the tumor’s blood supply. We speculate that decreasing the vascular network of vessels surrounding the tumor increases the accessibility of chemotherapy drugs to the primary tumor, which explains why D₂R agonist treatment sensitizes the SCLC to chemotherapeutic agents. This work has been supported by a Research Scholar Grant from the American Cancer Society. 

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 work was the first to show DARPP-32 isoforms promote non-small cell lung cancer (NSCLC) growth in orthotopic mouse models (Communications Biology, 2018). 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 (NPJ Precision Oncology, 2023). Elevated t-DARPP isoform expression in NSCLC was found to be associated with poor overall survival and increasing tumor (T) stage, based on bioinformatics analyses and immunohistochemistry studies using a large cohort of patient-derived lung adenocarcinoma specimens. We have demonstrated that DARPP-32 drives ERBB3-mediated resistance to molecular targeted therapy in lung adenocarcinoma (Oncogene, 2022). 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.

Patients with advanced NSCLC and mutations in epidermal growth factor receptor (EGFR) benefit from EGFR tyrosine kinase inhibitors (TKIs). Osimertinib, a third-generation EGFR TKI, is standard first-line therapy for EGFR-mutated NSCLC, but most patients develop resistance to it. We have recently shown that increased formation of primary cilia, microtubule-based sensory organelles, is associated with osimertinib-refractory NSCLC progression. Current studies are investigating how targeted inhibition of ciliogenesis may prevent or overcome osimertinib resistance.  

We are also investigating how cancer-promoting chemicals originating from vehicle emissions contribute to NSCLC initiation, progression, and metastasis. 

Education:

• 2010-2015: Postdoctoral Fellow, Mayo Clinic, Rochester, Minnesota (Mukhopadhyay Lab)
• 2004-2010: Ph.D. in Cancer Biology, University of Minnesota, Minneapolis, Minnesota (Westendorf Lab)
• 2000-2004: B.S. in Genetics & Life Sciences Communication, University of Wisconsin, Madison, Wisconsin

Primary Research Areas: 

• Cancer Biology
• Vascular Biology
• Molecular Biology 

Research Specialties:

• Therapy-refractory lung cancer progression 
• Vascular permeability 
• Mouse and zebrafish models of tissue injury, cancer, and metastasis 
• Tumor microenvironment and angiogenesis
• Metastasis

Selected Awards: 

• 2022-2026: Lung Cancer Research Foundation and EGFR Resisters Grant Awardee
• 2021-2025: American Cancer Society Research Scholar Grant Awardee
• 2020-2021: The Elsa U. Pardee Foundation Grant Awardee
• 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)

Identifying novel mechanisms of lung cancer progression and resistance:

1. Alam SK, Pandit A, Wang L, Mortazavi Farsani SS, Thiele BA, Manoj P, Aubry MC, Verma V, Rudin CM, Lo YC, Hoeppner LH. Dopamine D₂ receptor agonists abrogate neuroendocrine tumour angiogenesis to inhibit chemotherapy-refractory small cell lung cancer progression. Cell Death & Disease. 16(1):370; 2025. PMID: 40346068
2. Alam SK, Wang L, Zhu Z, Hoeppner LH. IKKα promotes lung adenocarcinoma growth through ERK signaling activation via DARPP-32-mediated inhibition of PP1 activity. NPJ Precision Oncology. 7(1):33; 2023. PMID: 36966223
3. Alam SK, Zhang Y, Wang L, Zhu Z, Hernandez CE, Zhou Y, Yang N, Lei J, Chen X, Zeng L, Klein MA, Hoeppner LH. DARPP-32 promotes ERBB3-mediated resistance to molecular targeted therapy in EGFR-mutated lung adenocarcinoma. Oncogene. 41(1):83-98; 2022. PMID: 34675407
4. 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 tumour cell proliferation. British Journal of Cancer. 123:819-832; 2020. PMID: 32499571
5. 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. 1:43; 2018. PMID: 29782621 
6. 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(1):270-81; 2015. PMID: 25226814 

Understanding the molecular regulation of vascular permeability: 

1. Han DJ, Sui X, Agarwal S, Sorayah R, Singhal A, Hoeppner LH, Oehlers SH. The repurposed STAT3 inhibitor pyrimethamine controls mycobacterial infection-induced vascular permeability and mycobacterial burden. Biomedicine & Pharmacotherapy. Oct:191:118464; 2025. PMID: 40803230
2. Phoenix KN, Yue Z, Yue L, Cronin CG, Liang BT, Hoeppner LH, Claffey KP. PLCβ2 Promotes VEGF-Induced Vascular Permeability. Arteriosclerosis, Thrombosis, and Vascular Biology. 42(10):1229-1241; 2022. PMID: 35861069
3. Wang L, Astone M, Alam SK, Zhu Z, Pei W, Frank DA, Burgess SM, Hoeppner LH. Suppressing STAT3 activity protects the endothelial barrier from VEGF-mediated vascular permeability. Disease Models & Mechanisms. 14(11): dmm049029; 2021. PMID: 34542605
4. 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

In vivo modeling of tissue injury:

1. Lawrence J, Seelig D, Demos-Davies K, Ferreira C, Ren Y, Wang L, Alam SK, Yang R, Guedes A, Craig A, Hoeppner LH. Radiation dermatitis in the hairless mouse model mimics human radiation dermatitis. Scientific Reports. 14(1):24819; 2024. PMID: 39438583
2. Hartono SP, Bedell VM, Alam SK, O'Gorman M, Serres M, Hall SR, Pal K, Kudgus RA, Mukherjee P, Seelig DM, Meves A, Mukhopadhyay D, Ekker SC, Hoeppner LH. Vascular Endothelial Growth Factor as an Immediate-Early Activator of Ultraviolet-Induced Skin Injury. Mayo Clinic Proceedings. 97(1):154-164; 2022. PMID: 34823856
3. Vohra PK, Hoeppner LH, Sagar G, Dutta SK, Misra S, Hubmayr RD, Mukhopadhyay D. Dopamine inhibits pulmonary edema through the VEGF-VEGFR2 axis in a murine model of acute lung injury. American Journal of Physiology Lung Cellular and Molecular Physiology. 302(2):L185-92; 2012. PMID: 22003095

In vivo modeling of cancer metastasis:

1. Ferrari MG, Jimenez-Uribe AP, Wang L, Hoeppner LH, Murugan P, Hahm E, Yu J, Kuzel TM, Gradilone SA, Mansini AP. Myeloid differentiation factor-2/LY96, a potential predictive biomarker of metastasis and poor outcomes in prostate cancer: clinical implications as a potential therapeutic target. Oncogene. 43(7):484-494; 2024. PMID: 38135694
2. 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. 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(24):6421-6432; 2018. PMID: 30087142.
3. 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

Complete publication list.