Jaime Modiano, VMD, PhD

Dr. Modiano completed his veterinary training and PhD in Immunology at the University of Pennsylvania in Philadelphia (1984-1991), followed by a residency in Veterinary Clinical Pathology at Colorado State University in Fort Collins, CO (1991-1993), and a post-doctoral fellowship at the National Jewish Medical and Research Center in Denver, CO. He was Assistant Professor of Veterinary Pathobiology at Texas A&M University between 1995 and 1999, returned to Denver from 1999 to 2007, where he held Scientist and Senior Scientist appointments at the AMC Cancer Research Center and was Associate Professor of Immunology and Full Member of the Cancer Center at the School of Medicine of the University of Colorado, Denver. Between 2001 and 2003, Dr. Modiano served as Director of Cancer Immunology and Immunotherapy for the Donald Monk Cancer Research Foundation; he also is a partner at Veterinary Research Associates, LLP, a company focused on development and implementation of diagnostics for veterinary medicine and a founder/scientist at ApopLogic Pharmaceuticals, Inc., a biotechnology company focused on development of cancer therapeutics. In July of 2007, Dr. Modiano joined the College of Veterinary Medicine and the Masonic Cancer Center, University of Minnesota, where he continues his research program as Professor of Comparative Oncology holding the Al and June Perlman Endowed Chair.

Modiano Lab Research Emphasis

The focus of my laboratory has been to understand cell growth regulation in the context of cancer pathogenesis, fostering an environment that spans basic to translational research.

Cancer Genetics: As part of large, multi-institutional collaborations, we have documented breed-specific risk factors for canine lymphoma, hemangiosarcoma, and osteosarcoma. We also have identified evolutionarily conserved, cancer-associated genomic changes cancer in humans and companion animals. Current efforts in this area are aimed at defining mechanisms responsible for cancer-specific mutations as well as conserved gene-environment interactions.

Cancer Immunology and Tumor-Microenvironment Interactions: It is now apparent that interactions between the tumor and its microenvironment are essential for tumor progression and tumor control. Our work is focused on understanding how altering specific components of the tumor microenvironment can respectively enhance tumor growth and survival or promote anti-tumor immunity, and thus delay or prevent progression and metastasis. Current efforts are aimed at understanding the role of innate immune factors in tumor engraftment and survival, as well as the contribution of stromal elements to the tumor immunosuppressive barrier.

Diagnostic Development: The extensive heterogeneity present within and among tumors presents a major contemporary challenge for effective cancer management. To overcome this, we have dedicated significant effort to develop robust schemes to classify tumors according to their biological behavior. We have used cellular, immunologic, and molecular tools, including genome-wide platforms and innovative bioinformatics, to design practical tests for tumor classification and monitoring. Several tests are the subject of patents and have been licensed for commercialization. Our ongoing work in this area seeks to improve on existing tests and on development of new predictive biomarkers that will help clinicians tailor patient-specific treatment strategies.

Therapeutic development: We have taken advantage of the conserved molecular signatures in spontaneous tumors of domestic animals to test new and innovative, targeted therapies. These studies include target validation in the laboratory, as well as pre-clinical and clinical development in our tumor-bearing veterinary patient populations. Recent and ongoing trials include evaluation of (1) gene-based immunotherapy platforms, (2) genetically engineered, ligand-targeted toxins, (3) enhanced anti-tumor immunity through passive immunotherapy, (4) small molecules, and (5) targeted nanoparticles for gene delivery.

These different aspects of work have been funded by the NIH and by various non-profit foundations. They include ongoing collaborations with scientists within and outside the United States.

• Murphy SE, et al. (2011). Chronic nicotine consumption does not influence 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis. Cancer Prev Res 4(11), 1752-1760.
• Ito D, et al. (2011). A lymphoid progenitor population in canine non-Hodgkin lymphoma. J Vet Intern Med, 25(4), 890-896.
• Scott MC, et al. (2011). Molecular subtypes of osteosarcoma identified by reducing tumor heterogeneity through an interspecies comparative approach. Bone, 49, 356-367. 
• Gu D, et al. (2012). Biomonitoring the cooked meat carcinogen 2-amino-1-methy-6-phenylimidazo[4,5-b]pyridine in canine fur. J Agric Food Chem, 60(36), 9371-9375.
• Modiano JF, et al. (2012). Inflammation, apoptosis, and necrosis induced by neoadjuvant Fas ligand gene therapy improve survival of dogs with spontaneous bone cancer. Mol Ther, 20, 2234-2243.
• Larson G, et al. (2012). Rethinking dog domestication by integrating genetics, archeology, and biogeography. Proc Natl Acad Sci, 109(23), 8878-83.
• Ito D, et al. (2012). CD40 ligand is necessary and sufficient to support primary diffuse large B-cell lymphoma cells in culture: a tool for in vitro preclinical studies with primary B-cell malignancies. Leuk Lymphoma, 53(7), 1390-1398.
• Thayanithy V, et al. (2012). Perturbation of 14q32 miRNAs-cMYC gene network in osteosarcoma. Bone 50, 171-181.
• Karlsson E, et al.(2013).Genome-wide association in three dog breeds identifies 33 osteosarcoma risk loci and implicates CDKN2A/B regulation as early driver of disease. Genome Biol, in press
• Koopmeiners JS, Modiano JF. (2013). Extending the TITE CRM to multiple outcomes with application to a phase 1 clinical trial in canine hemangiosarcoma. Clin Trials, 2013 Sep 30. [Epub ahead of print].
• Feeney DA, et al. (2013). Applicability of 3T body MRI in assessment of non-focal bone marrow involvement from hematopoietic neoplasia in dogs: A pilot study. J Vet Intern Med, 27(5):1165-71.
• Michael H, et al. (2013). Isolation and characterization of canine natural killer cells. Vet Immunol Immunopathol, 155(3), 211-217.
• Schappa JT, et al. (2013). Hemangiosarcoma and its cancer stem cell subpopulation are effectively killed by a toxin targeted through epidermal growth factor and urokinase receptors. Int J Cancer, 133(8), 1936-1944.
• Frantz AM, et al. (2013). Molecular profiling reveals prognostically significant subtypes of canine lymphoma. Vet Pathol 50(4), 693-703.
• Sarver AL, et al. (2013). MicroRNAs at 14q32 locus have prognostic significance in osteosarcoma. Orphanet J Rare Dis, 8(1), 7.
• Ito D, et al. (2014). Development of a novel anti-canine CD20 monoclonal antibody with diagnostic and therapeutic potential. Leuk Lymphoma, 16, 1-7. PMID: 24724777. PMCID: PMC5002357
• Ito D, et al. (2014). Canine lymphoma as a comparative model for human non-Hodgkin lymphoma: recent progress and applications. Vet Immunol Immunopathol, 159(3-4), 192-201. PMID: 24642290. PMCID: PMC4994713
• Gorden BH, et al. (2014). Identification of three molecular and functional subtypes in canine hemangiosarcoma through gene expression profiling and progenitor cell characterization. Am J Pathol, 184(4), 985-95. PMID: 24525151. PMCID: PMC3969990
• Scott MC, et al. (2015). Aberrant RB-E2F transcriptional regulation defines molecular phenotypes of osteosarcoma. J Biol Chem, 290(47), 28070-83. PMID: 26378234. PMCID: PMC4653667
• Tonomura N, et al. (2015). Genome-wide association study identifies shared risk loci common to two malignancies in golden retrievers. PLoS Genet, 11(2):e1004922. PMID: 25642983. PMCID: PMC4333733
• Moriarity BS, et al. (2015). A Sleeping Beauty forward genetic screen identifies genes promoting osteosarcoma development and metastasis. Nat Genet, 47(6), 615-24. PMID: 25961939. PMCID: PMC4767150
• Rodriguez AM, et al. (2015). Association of sphingosine-1-phosphate (S1P)/S1P receptor-1 pathway with cell proliferation and survival in canine hemangiosarcoma. J Vet Intern Med, 29(4), 1088-97. PMID: 26118793. PMCID: PMC4684944
• Im KS, et al. (2015). Interactions between CXCR4 and CXCL12 promote cell migration and invasion in canine hemangiosarcoma. Vet Comp Oncol, 2015 Sep 3. doi: 10.1111/vco.12165. [Epub ahead of print]. PMID: 26337509
• Elvers I, et al. (2015). Exome sequencing of lymphomas from three dog breeds reveals somatic mutation patterns reflecting genetic background. Genome Res, 25(11), 1634-45. PMID: 26377837. PMCID: PMC4617960
• Modiano JF, et al. (2015). Mesenchymal stromal cells inhibit anti-tumor immune responses by attenuating inflammation and reorganizing the tumor microenvironment. Cancer Immunol Immunother, 64(11), 1449-60. PMID: 26250807. PMCID: PMC4618101
• Scott MC, et al. (2016). Heterotypic models of osteosarcoma recapitulate tumor heterogeneity and biological behavior. Dis Model Mech, 9, 1435-1444. PMID: 27874835. PMCID: PMC5200896
• Modiano JF and Bellgrau D. (2016). Fas ligand based immunotherapy: A potent and effective neoadjuvant with checkpoint inhibitor properties, or a systemically toxic promoter of tumor growth? Discov Med, 21(114), 109-16. PMID: 27011046
• Weiskopf K, et al. (2016). Eradication of canine diffuse large B-cell lymphoma in a murine xenograft model with CD47 blockade and anti-CD20. Cancer Immunol Res, 4(12), 1072-1087. PMID: 27856424
• Seelig DM, et al. (2017). Constitutive activation of alternative nuclear factor kappa B pathway in canine diffuse large B-cell lymphoma contributes to tumor cell survival and is a target of new adjuvant therapies. Leuk Lymphoma, 58(7), 1702-1710. PMID: 27931134
• Borgatti A, et al. (2017). Evaluation of 18-F-fluoro-2-deoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) as a staging and monitoring tool for dogs with stage-2 splenic hemangiosarcoma – A pilot study. PLoS ONE 12(2), e0172651. doi:10.1371/journal.pone.0172651. PMID: 28222142
• Borgatti A, et al. (2017). Safe and effective sarcoma therapy through bispecific targeting of EGFR and uPAR. Mol Cancer Ther, 2017 Feb 13. pii: molcanther.0637.2016. doi: 10.1158/1535-7163.MCT-16-0637. [Epub ahead of print]. PMID: 28193671

Complete list of Dr. Modiano's publications available through PubMed.