2018-19 ANNUAL REPORT Structural Biology of Membrane Transport 4 Molecular Bioengineering and Cancer Vaccine 6 MESSAGE FROM THE EXECUTIVE DIRECTOR PG 3 Membrane Biochemistry and Molecular Biophysics 8 Cancer Stem Cells and Necroptosis 10 Today The Hormel Institute, University of Minnesota is a prominent cancer and chronic disease Genome Instability & Chromosome Biology 12 research center and high performing part of the Masonic Cancer Center. DNA Repair & Genome Stability 14 After two major expansions in 11 years, The Hormel Institute is home to some of the world’s Cellular and Molecular Biology 16 expert cancer researchers, a stunning design for our cancer center, and labs filled with state of the art technologies. Cell Death and Cancer Genetics 18 Cancer Cell Biology and Translational Research 20 We are focused on accelerating answers to cancer and other chronic diseases so people can live OF MINNESOTA UNIVERSITY longer, healthier lives. The Hormel Institute is currently comprised of 140 faculty, researchers, Cellular Dynamics 22 and staff. We now have 19 research sections with plans to continue to fill the institute’s labs with // TABLE OF CONTENTS TABLE expert scientists to further our mission. In fact, two more research sections will be added in the Cancer Biology 24 late fall of 2019. Tumor Microenvironment and Metastasis 26 After joining The Hormel Institute in 1999, I have had a great and incredible journey with Transcription and Gene Regulation 28 Inside front cover The Hormel Institute faculty and staff to help build The Hormel Institute, University of Minnesota, Chromatin and Epigenetic Gene Regulation 30 Accelerating ANSWERS to where we are today. Cancer Epigenetics and Experimental Therapeutics 32 Strengthened by leadership and support from the University of Minnesota, The Hormel Foundation, to CANCER and our generous community, we are fully committed to enhancing and maintaining our quest for THE HORMEL INSTITUTE Cryo-EM and Molecular Cell Biology 34 continued success through discoveries leading to cancer prevention and healthier controls. Stem Cells and Cancer 36 MISSION STATEMENT I’m honored to serve as interim executive director and I thank you - on behalf of all of Cell Signaling and Tumorigenesis 38 The Hormel Institute, UMN - for your continued support. Computational Cancer Genomics 40 The mission of The Hormel Institute is to conduct research and provide education in the biological sciences with applications Supporting Departments 42 Sincerely, in medicine and agriculture. In pursuit of this mission, and Partners in Growth 46 as intended by itsMISSION founders, The STATEMENT Hormel Institute generates Today’s EDUCATION, Tomorrow’s DISCOVERIES 48 fundamental knowledge and disseminates it to the scientific community worldwide. It also serves as a center of technical Ann M. Bode, Ph.D. and educational expertise for the benefit of the Austin Interim Executive Director community, the surrounding region and the State of Minnesota. Structural Biology of Membrane Transport Amer Alam, Ph.D. nanometer resolution). This allows for accurate Primary Research Areas: visualization of the molecular details underlying PG 4 PG 5 1) Membrane transport processes the functioning of macromolecules­­­ and has SECTION LEADER / ASSISTANT PROFESSOR 2) Peroxisome biogenesis and revolutionized structural biology and allowed homeostasis for targeting of complex biological problems 3) Lipid/protein interactions previously considered off-limits to high resolution 4) Lipid and fatty acid metabolism visualization Such insight is invaluable in obtaining molecular details of membrane protein interactions with drugs, transport substrates, pathologies ranging from rare inherited and inhibitors and can aid in the design of novel diseases such as Zellweger’s syndrome therapeutics targeting diseases stemming from UNIVERSITY OF MINNESOTA OF MINNESOTA UNIVERSITY and adrenoleukodystrphy (both stemming membrane protein dysfunction. OF MINNESOTA UNIVERSITY from peroxisomal dysfunction) to a range // // of neurodegenerative disorders, diabetes, and cancer. Research Specialties: 1) Membrane protein biochemistry The Hormel Institute ranks amongst 2) Cryo electron microscopy a handful of elite institutions housing 3) X-ray crystallography a Titan Krios microscope combined with a direct electron detector, a setup designed to obtain near-atomic resolution (routinely achieving better than 0.5 FROM LEFT TO RIGHT: THE HORMEL INSTITUTE THE HORMEL INSTITUTE Mehedi Hasan, Amer Alam, James Thompson THE HORMEL INSTITUTE Summary npj PRECISION ONCOLOGY The Alam lab uses a combination of - Springer Nature launched the journal “npj Precision Oncology” in partnership with The Hormel Institute, University of Minnesota in Austin, Minnesota, United States. biochemical and structural (Cryo-EM and X-ray - npj Precision Oncology, is a new open access, international, peer-reviewed journal that publishes cutting edge scientific research in all aspects of precision oncology, from basic crystallography) techniques to primarily study science to translational applications to clinical medicine. macromolecules and macromolecular complexes - The journal defines precision oncology as cancer diagnosis, prevention, and/or treatment tailored specifically to the individual patient based on their genetic and/or molecular profile. involved in membrane transport, homeostasis, - npj Precision Oncology fills the need of a journal where both preclinical and early clinical studies can be published together to help support this rapidly advancing field. and biogenesis, with a particular focus on - According to the Managing Editor at Nature Research “Npj Precision Oncology has been exceptionally successful”. We have passed the first landmark of 25 peer-reviewed published pinpointing lipid/protein interactions in context articles, which makes our journal eligible to apply for inclusion in PUBMED, one of the first steps required to obtain an IMPACT FACTOR. We are also looking for 1-2 additional of membrane protein function. Maintenance of Associate Editors to bring on board. membrane bilayer integrity and tight control over - Featured topics include cancer development and prevention, therapies that target specific cellular pathways, cancer metabolism and genetic risk factors. material transfer across cellular and organellar - In addition to publishing original basic science, translational and clinical research articles, npj Precision Oncology -also publishes case reports, brief communications, commentaries, membranes is central to proper physiological perspectives, and review articles. functioning. Dysfunction of these systems lies - The journal also publishes a professionally written Editorial Lay Summary to accompany each research Article, which summarizes the key issues being addressed within the article at the heart of several devastating, often fatal aimed to keep readership at the vanguard of new discoveries in the field. Please visit us at: https://www.nature.com/npjprecisiononcology/ Molecular Bioengineering and Cancer Vaccine George Aslanidi, Ph.D. NK cells. Consequently, we showed that tumor- Additionally, we plan to test our anti-cancer vacci- infiltrated lymphocytes displaying increased nation approach in companion dogs with sponta- PG 6 “Our lab develops a safe and effective antigen-based PG 7 expression of PD-1 should sensitize tumor to neous melanoma. Importantly, companion dogs SECTION LEADER / ASSOCIATE PROFESSOR vaccination strategy to activate patience immune aPD-1 therapy. Indeed, use AAV based vaccination are exposed to the same environmental factors, system and redirect it to kill cancer cells.” in combination with aPD-1 treatment significantly and are developing cancer with clinical patholo- George Aslanidi delayed tumor development and extend in vivo gy very similar to humans. This makes dogs the model survival. Therefore, the path forward most adequate preclinical model to evaluate the that we are planning to implement in our future efficacy of our anti-cancer vaccination. Testing studies to completely eradicate tumor, is multi- of our vaccine on clinically relevant dog patients target vaccination in concert with other therapies will not only help to extend the life of people’s best Our research has demonstrated that a strong that target tumor microenvironment and re- friends, but provide critical data ensuring progress antigen-specific immune response is developed UNIVERSITY OF MINNESOTA OF MINNESOTA UNIVERSITY activate/support immune cells infiltrating tumor. into clinical application for humans is warranted. OF MINNESOTA UNIVERSITY after a single injection of AAV-based vaccine // in in vivo model. We attribute this to our novel // capsid-optimized AAV based system, which has overcome many of the shortcomings of past viral cancer vaccine technologies: the precise modifications in the AAV capsid significantly increase transduction efficiency of the APCs CD11c+/MHC II+ and subsequent antigen presentation. In current S669 S663 studies we further optimized AAV expression T665 Improved K66 cassette by fusing antigen with MHC class I intracellular 6 T251 molecule trafficking signals. This modification THE HORMEL INSTITUTE THE HORMEL INSTITUTE trafficking THE HORMEL INSTITUTE T722 HI loop escape from endosome significantly increased AAV mediated level of K707 S47 S492 T492 both antigen-specific CD8+ T and CD4+ T cells, Y705 Y73 9 1 K53 enhanced the formation of effector memory Summary 1 precursor (CD 62L-/CD127+) cells which ensure Y445 We currently use our bioengineered capsid-