2014-2015 Hormel Institute Annual Report

Total Page:16

File Type:pdf, Size:1020Kb

2014-2015 Hormel Institute Annual Report PRSRT STD U.S. POSTAGE PAID Permit No. 32 Austin, MN 801 16th Avenue N.E. Austin, MN 55912-3679 Return Service Requested The research, partnerships and resources of The Hormel Institute are dedicated to a single purpose: Improving health through medical research. Today’s RESEARCH, Tomorrow’s CURES www.hi.umn.edu Cellular and Molecular Biology 6 Cancer Biomarkers and Drug Resistance 10 Molecular Chemoprevention and Therapeutics 12 Membrane Biochemistry 16 Structural Biology 20 The mission of The Hormel Institute is to conduct research and provide education Nutrition and Metabolism 22 Cell Death and Cancer Genetics 24 in the biological sciences with applications in medicine and agriculture. In pursuit Cancer Cell Biology and Translational Research 28 Today’s RESEARCH, of this mission, and as intended by its founders, The Hormel Institute generates Cellular Dynamics 30 fundamental knowledge and disseminates it to the scientific community worldwide. Tumor Microenvironment and Metastasis 34 Tomorrow’s CURES It also serves as a center of technical and educational expertise for the benefit of Immunoregulation of Autoimmune Diseases and Cancer 36 Translational Cancer Research 37 the Austin community, the surrounding region and the State of Minnesota. Cancer Epigenetics & Experimental Therapeutics 38 Stem Cells and Cancer 42 Cell Signaling and Tumorigenesis Section 44 Partners in Growth 49 Expansion 2014 - 16 54 2 The Hormel Institute “Today’s Research, Tomorrow’s Cures.” 3 Message from the Executive Director Dr. Zigang Dong During the 2014-15 year, we continued our focus on cancer research technology. Both additions are scheduled for completion by January 2016. because cancer already has surpassed heart disease as the No. 1 killer All of us from The Hormel Institute are very thankful for the generous of Americans under age 80. In fact, cancer is the leading cause of death support from the State of Minnesota, The Hormel Foundation, Hormel worldwide. Cancer affects all of us: women and men; poor and rich; old Foods Corporation, University of Minnesota, Mayo Clinic, 5th District and young; and all races. Eagles Cancer Telethon, Paint the Town Pink, and many other individuals and groups. In particular, I would like to thank Mr. Gary Ray, Mr. Jeff The Hormel Institute is a leading medical research institute making Ettinger, Mr. Richard Knowlton, Mr. Joel Johnson, Mrs. Bonnie Rietz, Mr. contributions to the identification and discovery of novel targets and Jerry Anfinson, and Mr. Steve Rizzi. We thank Drs. Eric Kaler and Brian agents for cancer prevention and therapy. We experienced continued Herman (University of Minnesota); and Drs. John Noseworthy, Glenn success during 2014-2015 in obtaining research funding and producing Forbes, Robert Diasio, and Greg Gores (Mayo Clinic) for their leadership major research breakthroughs, even in a national environment of overall and support. We thank our elected leaders, Minnesota Governor Mark decreased funding for research. Dayton; U.S. Senators Amy Klobuchar and Al Franken; U.S. Representative Tim Walz; Minnesota State Senator Dan Sparks; Minnesota State On May 28, 2014, we finished the design of a new building expansion and Representative Jeanne Poppe; Minnesota State Senator David Senjem; and held a groundbreaking ceremony with numerous local, state, and national Austin Mayor Tom Stiehm for their continued support. We remain deeply leaders. This 20-laboratory expansion is funded in part by $13.5 million grateful to our community, our partners, and our collaborators for giving in State of Minnesota bonding funds included in a bill supported by State us the gift of being able to work here. Their support and gifts allow today’s Senator Dan Sparks and State Representative Jeanne Poppe, and signed research to flourish and pave the way for tomorrow’s progress to continue. by Governor Mark Dayton. The Hormel Foundation matched the state’s $13.5 million commitment to construct the laboratory space on our east side and was a major contributor to the $4.5 million Live Learning Center “Most human cancers are preventable, or on our west side, featuring a multi-purpose room and 250-seat lecture treatable, if discovered at an early stage.” hall with theater-style seating and state-of-the-art global communications Dr. Zigang Dong Executive Director support 4 The Hormel Institute “Today’s Research, Tomorrow’s Cures.” 5 Cellular and Molecular Biology constitute a family of protein kinases that mediate signal transduction volume in a solar UV-induced skin carcinogenesis mouse model. A substantial Zigang Dong, M.D., Dr. P.H. downstream of the MAPK cascades. Phosphorylation of RSK and MSK1 reduction of phosphorylation in mitogen-activated protein kinase signaling Executive Director/Section Leader can be attenuated by aspirin intake. The widespread over-expression of was upregulated in human squamous cell carcinoma (SCC) and SUV-treated was observed in mice treated with caffeic acid either before or after solar UV McKnight Presidential Professor in Cancer Prevention EGFR occurs as a consequence of COX-2 activation in familial adenomatous mouse skin. Kaempferol – a natural flavonol found in tea, broccoli, grapes, exposure. Caffeic acid directly interacted with ERK1/2 and inhibited ERK1/2 Hormel/Knowlton Professor polyposis (FAP) patients. This study revealed a functional association between apples, and other plant sources – is known to have anticancer activity, but its activities in vitro. Importantly, we resolved the co-crystal structure of ERK2 COX-2 and EGFR expression during colon carcinogenesis and mechanisms and direct target(s) in cancer chemoprevention are unclear. Kinase provided new strategies for colon cancer prevention and therapy. array results revealed that kaempferol inhibited RSK2 and MSK1. Pull-down b. Discovery of novel mechanisms of RNF2 in cell death. assay results, ATP competition, and in vitro kinase assay data revealed that RNF2, also known as Ring1B/Ring2, is a component of the kaempferol interacts with RSK2 and MSK1 at the ATP-binding pocket and polycomb repression complex 1. RNF2 is highly expressed in inhibits their respective kinase activities. Mechanistic investigations showed many tumors, suggesting it might have an oncogenic function, that kaempferol suppresses RSK2 and MSK1 kinase activities to attenuate but the mechanism of action is unknown. We showed that SUV-induced phosphorylation of cAMP-responsive element binding protein knocking down RNF2 expression significantly inhibits both (CREB) and histone H3 in mouse skin cells. Kaempferol was a potent inhibitor cell proliferation and colony formation in soft agar and induces of SUV-induced mouse skin carcinogenesis. Further analysis showed that skin apoptosis in cancer cells. Knockdown of RNF2 in HCT116 from the kaempferol-treated mice exhibited a substantial reduction in SUV- p53+/+ cells resulted in significantly more apoptosis than was induced phosphorylation of CREB, c-Fos, and histone H3. Overall, our results observed in RNF2 knockdown HCT116 p53−/− cells, indicating identify kaempferol as a safe and novel chemopreventive agent against SUV- that RNF2 knockdown-induced apoptosis is at least partially, induced skin carcinogenesis that acts by targeting RSK2 and MSK1. dependent on p53. Various p53-targeted genes were increased in RNF2 knockdown cells. Further studies revealed that in RNF2 Chrysin (5,7-dihydroxyflavone), a natural flavonoid widely distributed in knockdown cells, the p53 protein level was increased, the half-life plants, reportedly has chemopreventive properties against various cancers. of p53 was prolonged, and p53 ubiquitination was decreased. The anti-cancer activity of chrysin observed in vivo studies, however, has (Left to right) Front row: Ann M. Bode, Ge Gao, Naomi Hamada, Qiushi Wang, Eunmiri Roh, Do Young Lim, Tatyana Zykova, Many proteins are Cancer is one of the leading causes of human In contrast, cells over-expressing RNF2 showed a decreased been disappointing. A chrysin derivative, referred to as compound 69407, Seung Ho Shin, Zigang Dong overexpressed only in cancer. death worldwide. By focusing on molecular p53 protein level, a shorter p53 half-life, and increased p53 ubiquitination. more strongly inhibited EGF-induced neoplastic transformation of JB6 P+ cells The epidermal growth factor mechanisms, we continue to discover the Importantly, we found that RNF2 directly binds with both p53 and MDM2 as compared with chrysin. It attenuated cell-cycle progression of EGF-stimulated Second row: Hanyong Chen, Ke Yao, Srinivasa Reddy Kanamata Reddy, Lichan Chen, Chengcheng Shi, Yi Zhang (green) is highly expressed key molecular events in cancer development well as promotes MDM2-mediated p53 ubiquitination. RNF2 over-expression cells at the G1 phase and inhibited the G1/S transition. Compound 69407 in skin tumors and is a major Third row: Yan Li, Wei He, JongBin Kim, Kun Yeong Lee, Sung-Young Lee, Margarita Malakhova, Wei Ya Ma as well as agents for cancer prevention and also could increase the half-life of MDM2 and inhibit its ubiquitination. The reduced tumor growth in the A431 mouse xenograft model and retinoblastoma Fourth row: KiBeom Bae, Joohyun Ryu, Hong-Gyum Kim, Hiroyuki Yamamoto, Tianshun Zhang, Tae-Gyu Lim. chemotherapy target in therapy. regulation of p53 and MDM2 stability by RNF2 also was observed during the phosphorylation at Ser795 and Ser807/811. Overall results indicated that breast cancer. compound 69407 is an ATP-noncompetitive cyclin-dependent kinase inhibitor Not pictured: Xiaoyu Chang,
Recommended publications
  • Inst Annual Report 2014
    PRSRT STD U.S. POSTAGE PAID 801 16 TH AVENUE N.E. • A USTIN , MN 55912-3679 Permit No. 32 Austin, MN Return Service Requested The research, partnerships and resources of The Hormel Institute are dedicated to a single purpose: Improving health through medical research. Toda y’s RESEARCH , Tomorro w’s CURES www.hi.umn.edu Cellular and Molecular Biology 6 Molecular Chemoprevention 10 and Therapeutics Cancer Biomarkers and 14 The mission of The Hormel Institute is to conduct research and Drug Resistance Membrane Biochemistry 16 provide education in the biological sciences with applications in Structural Biology 18 medicine and agriculture. In pursuit of this mission, and as Nutrition and Metabolism 20 Cell Death and Cancer Genetics 22 intended by its founders, The Hormel Institute generates Cellular Dynamics 24 Toda y’s RESEARCH, Tumor Microenvironment and Metastasis 28 Tomorro w’s CURES fundamental knowledge and disseminates it to the scientific Immunoregulation of Autoimmune 30 Diseases and Cancer community worldwide. It also serves as a center of technical Translational Cancer Research 32 and educational expertise for the benefit of the Austin community , Cancer Epigenetics & 34 Experimental Therapeutics the surrounding region and the State of Minnesota. Stem Cells and Cancer 36 Partners in Growth 40 Expansion 2014 - 16 46 2 3 Message from the Director Dr. Zigang Dong Cancer affects all of humankind: women and men, poor and rich, old and young, comprehensive study of human diseases by combining analysis of protein and all races. Cancer is the leading cause of death worldwide. Most human cancers structure/function with advanced methods of data management and drug screening.
    [Show full text]
  • January 2019 Moccasin Flower
    “Rotary- neighbors, friends, and problem-solvers who come together to make positive, lasting change in communities at home and abroad.” Moccasin Flower Official Publication of The Rotary Club of Rochester, Minnesota Club No. 2164 Organized June 12, 1925 District No. 5960 Volume 91 January 2019 Number 7 VITAL STATISTICS JANUARY BIRTHDAYS ROCHESTER ROTARY RISERS: none reported Name Birthday Birthplace GREATER ROCHESTER ROTARY: none reported January 1 Mark Benscoter Rochester, MN ROTARY eCLUB ONE: none reported Ellen Wells Minneapolis, MN OTHER CLUBS: none reported January 4 Wes Duellman Winona, MN NEW MEMBERS: Josh Noser Sue M. Johnson Rochester, MN 2019 MEETING LOCATION January 11 Jennifer Teske Hampton, IA January 24 Walt Menning LaSalle, IL AND MEAL COSTS January 25 Kathy Lessard Osage, IA President Sara Gilliland January 27 Bri Hightshoe Yuma, AZ Thanks to those members January 30 Donna Greason New York who completed the survey that was emailed in Melody Trimble KI Sawyer AFB, MI September, asking for your January 31 Deb Muench Sparta, WI input on the logistics of our traditional meetings. If we have misprinted or missed your birthday, The majority of the survey respondents preferred a please contact the Rotary office. downtown location, a Thursday noon meeting and better parking options. That’s a tall order! The board requested bids from downtown venues and caterers. Then, the Board reviewed the bids, deliberated about the available choices, and selected the most reasonable cost option available. Mayo Civic Center will continue in 2019 as the main location for traditional meetings on the 2nd, 4th and 5th Thursdays of most months.
    [Show full text]
  • Inst Annual Report 2013
    Cellular and Molecular Biology 6 Membrane Biochemistry 10 Nutrition and Metabolism 12 Cell Death and Cancer Genetics 14 Cellular Dynamics 16 Stem Cells and Cancer 20 Immunoregulation of Autoimmune 22 Today ’s RESEARCH Diseases and Cancer Tomorrow’s Cancer Epigenetics & 24 CURES Experimental Therapeutics Structural Biology 26 Molecular Chemoprevention 28 and Therapeutics Cancer Biomarkers and 32 Drug Resistance Translational Cancer Research 34 Partners in Growth 44 2 The mission of The Hormel Institute is to conduct research and provide education in the biological sciences with applications in medicine and agriculture. In pursuit of this mission, and as intended by its founders, The Hormel Institute generates fundamental knowledge and disseminates it to the scientific community worldwide. It also serves as a center of technical and educational expertise for the benefit of the Austin community, the surrounding region and the State of Minnesota. 3 “Most human cancers are preventable, or treatable, if discovered at an early stage.” 4 Message from the Director Dr. Zigang Dong Even though the total number of deaths due to cancer in the United States is The ICRT is a collaborative project with manufacturers of technology, such as declining, cancer is still the leading cause of death worldwide. Most human cancers IBM Rochester, to develop new technology to accelerate discovery and facilitate are preventable or treatable if discovered at an early stage. The Hormel Institute the comprehensive study of human diseases by combining analysis of protein struc- is a leading medical research institute making major contributions to the identification ture/function with advanced methods of data management and drug screening.
    [Show full text]
  • Destination Medical Center Corporation Board of Directors
    Destination Medical Center Corporation Board of Directors Meeting Thursday, May 23, 2019 9:30 A.M. Mayo Civic Center Rochester, Minnesota DESTINATION MEDICAL CENTER CORPORATION (DMCC) BOARD MEETING Thursday, May 23, 2019 9:30 A.M. AGENDA PAGE I. Call to Order II. Roll Call III. Approval of Agenda 1 IV. Approval of Minutes: February 5, 2019 3 V. Public Comment Period VI. Chair’s Report A. Appointment of Secretary VII. DMC Metrics: Update 7 VIII. Consent Agenda A. Certification of Expenditures to DEED 11 Resolution A: Ratifying and Confirming the Revised April 1 Report to DEED Pursuant to Statute B. Commending Dana Bailey 25 Resolution B: Commending Dana Bailey for Her Service C. Amendment to Working Capital Loan 27 Resolution C: Approving the First Amendment to and Execution of Amendments to Working Capital Loans IX. DMCC Audit for Year Ending December 31, 2018 29 (Presenter: Craig Popenhagen, CliftonLarsonAllen) 1 X. 2020 DMCC Funding Request: Process and Timeline 67 XI. Affordable Housing Update 71 (Presenters: Terry Spaeth, City; Dave Dunn, Olmsted County; Kevin Bright, EDA; Jennifer Woodford or Steve Borchardt, Rochester Area Foundation) XII. Project Updates (City of Rochester, EDA) A. Transportation 73 B. Heart of the City 77 Resolution D: Approving Design Development for the Heart of the City Project C. Chateau Theatre 81 D. Discovery Square 83 XIII. Energy Integration Committee 85 Resolution E: Receiving Energy Integration Committee Materials and Affirming Goals XIV. EDA Update A. Experience Update 123 B. Development Plan 5 Year Update 125 C. Market Studies 127 D. Riverfront: Next Steps 129 XV. DMCC 2019 Budget: Year to Date Update 147 XVI.
    [Show full text]
  • Departmental Offices, FOIA Log October 1 - December 31, 2018 Requestor Organization Request # Short Description Request Type
    Departmental Offices, FOIA Log October 1 - December 31, 2018 Requestor Organization Request # Short Description Request Type Johnston, Julie Private Citizen 2018-10-003 Requests information published on 11/16/17 by Susan Tsui Grundsmann of the FOIA Office of Compliance, the names of the people we, the taxpayers, have paid awards and settlements under the CAA. Preble, Keith University at Albany, SUNY 2018-10-008 Requests a list of all OFAC cases/investigations from 2003-2017 that did not result in FOIA any enforcement action or settlement against individuals or entity. I would also request that if such information is provided and released that any data provided contain the same information that is released under “31 CFR 501.805 - Rules governing availability of information.” (b) (6) 2018-10-009 Requests any documents that show (b) (6) prior (b) (6) FOIA from 1995-2009. Ramirez, Ronnie 2018-10-010 Requests US Treasury Audit of ALL garnishments and offsets by TOP, to include IRS FOIA interceptions, Retro-pays and stimulus payments. Prior requests have been referred to Debt Management Center. Requests Dates of garnishments, amounts, agency paid -Request dates of payments to agency from pension payments, amounts, and agency paid -Request list of payments withheld from pension and paid directly to Veterans Administration for repayment of debt with dates, amounts and running totals. Everson, Zach The Daily Beast 2018-10-011 Requests all correspondence, letters, emails, texts, faxes, telephone messages, FOIA voicemail messages, transcripts, notes, or minute of any meetings, telephone conversations, discussions, and attachments to emails or other records re: Craig Phillips' (Counselor to the Secretary) visit to the Trump International Hotel, Washington, D.C.
    [Show full text]
  • 2014 Department Convention Issue the Minnesota American Legion and Auxiliary
    2014 Department Convention Issue The Minnesota American Legion and Auxiliary LegionnaireVolume 96, Number 7 For God and Country July 2014 Moon, Schaffer square off for 2014-15 Minneapolis Department Commander position This year’s Department convention will feature a con- test for state commander between Mike Schaffer of Fulda VA director: and Peggy Moon of St. Joseph. It will be the only contested election for a Legion offi- cer at the convention, which will be held July 17-19 at Rochester. Support is On the Auxiliary side, which for several years has fea- tured a contested election for second vice president, there is one candidate, Carol Kottom of Buffalo. still strong The convention will kick off with activities on By Al Zdon Wednesday, July 16. The American Legion Executive To put it all in perspective, while the ongoing VA inves- Committee will meet at 7 p.m. at the Marriott Hotel. tigations are casting the national veterans’ health care On the Auxiliary side, there will be a series of meet- agency in a negative light, the VA health care offered local- ings during Wednesday including the executive commit- ly is regarded as still quite good. tee at 1 p.m. at the Windsor Hall III at the Kahler Grand Beginning with the scandal in Phoenix, where VA offi- Hotel. There will be a reception for Northwest Division cials apparently lied about wait list problems, every day National Vice President Patricia Steranka of Colorado at seems to bring a new headline about poor performance by 7 p.m. Wednesday in the Elizabethan Ballroom at the the VA.
    [Show full text]
  • Destination Medical Center Corporation Board of Directors Meeting Agenda
    DESTINATION MEDICAL CENTER CORPORATION BOARD OF DIRECTORS MEETING AGENDA SEPTEMBER 26, 2013; MEETING NO 3; 9:00AM -12:00 PM 1. APPROVAL OF CONSENT AGENDA • Approve meeting minutes from August 9, 2013 and September 20, 2013 2. CHAIRS REPORT • Update on outside Legal Counsel 3. REPORT FROM ECONOMIC DEVELOPMENT AGENCY • Dr. Patricia Simmons from Mayo Clinic to update on formation of Economic Development Agency 4. DISCUSSION/ ACTION ITEMS • Overview of Development Plan • Approval of Resolution authorizing Board Chair to negotiate for Destination Medical Services with the Economic Development Agency for final approval by the Board • Approval of Resolution authorizing Board Chair to negotiate an operating services contract with the City of Rochester for final approval by the Board 5. OTHER BUSINESS • Approve DMCC Board meeting schedule through 2014 • Appointment of Secretary to DMCC (Unapproved) DESTINATION MEDICAL CENTER CORPORATION BOARD MEETING Meeting No. 1 August9, 2013 Governor Mark Dayton called the meeting to order at 2:00 PM in the Mayo Civic Center Ballroom at 30 Civic Center Drive SE, Rochester, Minnesota. Members Present: James V. Bier, Ardell F. Brede, James R. Campbell, William George, Ed Hruska, Susan Park Rani, and Tina Smith. Absent: R.T. Rybak. Governor Dayton expressed what a momentous day this is for Rochester and the entire State of Minnesota and also his gratitude to Dr. Noseworthyand the leadership of the Mayo Clinic for giving the State this phenomenal opportunity. He also thanked the leadership on the public side who assisted the State in taking advantage of this great opportunity and the legislators, both DFL and Republican, that worked to make this project a reality.
    [Show full text]
  • Destination Medical Center Corporation (Dmcc)
    DESTINATION MEDICAL CENTER CORPORATION (DMCC) BOARD MEETING 2 P.M. FRIDAY, AUGUST 9, 2013 ROCHESTER CONVENTION CENTER Destination Medical Center Corporation (DMCC) Board Meeting Friday, August 9, 2-4 p.m. Rochester Convention Center Grand Ballroom AGENDA I. Call Meeting to Order/Welcome - Governor Mark Dayton II. Official Welcome A. Mayor Ardell Brede, City of Rochester B. Jim Bier, Chairman, Olmsted County Board of Commissioners C. Dr. John H. Noseworthy, President and CEO, Mayo Clinic III. Board Introductions IV. Mayo Clinic/DMC Overview, Key Tasks A. Dr. John H. Noseworthy, President and CEO, Mayo Clinic B. Dr. Bradly Narr, Medical Director, DMC C. Lisa Clarke, Administrator, DMC V. General Business A. Election of DMCC Board Chair B. DMCC Meeting Schedule C. Process/Timeline to Select Legal Counsel, Process/Timeline for Review and Approval of Articles of Incorporation and Bylaws D. Identify Process/Timing for Drafting Policies and Procedures VI. Overview/Discussion of Open Meetings Law A. Terry Adkins, Rochester City Attorney VII. Meeting Adjourn Board Members James Vincent (Jim) Bier Chairman, Olmsted County Board of Commissioners Jim Bier was born in Janesville, Wis. He has a B.S. in Plant Pathology from the University of Wisconsin-Madison. He is married with three children. Mr. Bier has been a farmer since 1994 and a tax preparer since 2002 for Smith Schafer and Associates. From 1979-1991, he was Plant Superintendent for Seneca/Libby, managing daily operations for vegetable canning and freezing. From 1991-1994, he was a Commodity Buyer for Crenlo Manufacturing, purchasing contract material for tractor cab manufacturing and electronics.
    [Show full text]
  • Is for Bicycling
    March 2016 TheS Quarterlyhift Newsletter of the Bicycle Alliance of Minnesota winter... IS FOR BICYCLING at the Winter Cycling Congress Bike Parade Griffin Photo by Walter by Shawna MullenEardley, Congress’ vision of winter biking as a normal winter upon my return to Duluth was to start something Active Transportation Coordinator, Duluth YMCA activity become reality? fun to embrace the awesomeness of winter: an ice & BikeMN Board Member skating get-together at the ice rink near downtown We stop making it about biking! Genius, right? As to get people out of their cubicles during their I’m not the crazy bike lady that everyone in Timo Perälä, founder of the event, said in his opening lunch breaks. (There were also a lot of inspirational Duluth thinks I am! remarks, “We don’t have cyclists in Finland. We just examples at the WCC of communities embracing have people. A lot of them ride a bike every day. If winter in ways besides bicycling.) Only two friends That was my first thought as I wheeled my bike to the you say you’re a cyclist, you’ll hear, ‘Oh, do you race showed up, and I thought, “Two people! Perfect! chock-full bike parking area at the Winter Cycling or something?’” At the WCC, we heard about some We’re on the verge of something magnificent here!” Congress in early February. We were in the midst of impressive campaigns and events starting up just And as we skated around, the 3 of us brewed up an extraordinary blizzard, yet here at the venue and because they were fun.
    [Show full text]