What We Do
Our main research objectives are to elucidate the mechanisms regulating the normal development of the mammary gland and pancreas and to identify genetic pathways that control the development of breast and pancreatic cancer.
Numerous genes have been identified that are crucial for normal development and cancer. Their role is being studied in our research group through their deregulated expression in transgenic animals and through their deletion from the mouse genome by homologous recombination. Specifically, our laboratory has the expertise to overexpress genes in a temporally and spatially controlled manner using the tet system and to delete genes in a tissue-specific and temporally controlled fashion using the Cre/loxP recombination system. Current projects include the analysis of cytokine signaling through the Jak/Stat and PI3K/Akt pathways as well as the role of c-Myc and oncogenic Kras in the initiation and maintenance of pancreatic ductal adenocarcinoma.
Milestones of our research
Generation of the first genetically engineered mice that allow somatic gene deletions in the mammary gland [Abstract]
Generation of the first mouse model for a hereditary form of human breast cancer through mammary-specific deletion of the Brca1 gene (a collaboration with researchers at the NIDDK) [Abstract]
Defining the role of the Bcl-x gene in erythropoiesis (Bcl-x conditional knockout) [Abstract]
Discovery of a new mammary epithelial population in parous animals (PI-MECs), which when transplanted has certain features of multipotent mammary gland progenitors [Abstract]
Defining the biological role of Tsg101 in vivo (conventional and mammary-specific knockout); Tsg101 is essential for cell proliferation and cell survival; however, in contrast to previous reports Tsg101 is not a tumor suppressor gene for sporadic forms of breast cancer [Abstract]
Defining the role of Jak2 during mammary development (Jak2 conditional knockout) [Abstract]
Parity-induced mammary epithelial cells (PI-MECs) facilitate tumorigenesis in selected transgenic mouse models. [Abstract]
Expression of the Whey Acidic Protein (Wap) is necessary for adequate nourishment of the offspring but not functional differentiation of mammary epithelial cells [Abstract]
Parity-induced mammary epithelial cells (PI-MECs) are multipotent and express cell surface markers associated with stem cells [Abstract]
The Janus kinase 2 (Jak2) is required for expression and nuclear accumulation of Cyclin D1 in proliferating mammary epithelial cells [Abstract]
Generation of Wap-rtTA knockin mice that allow a ligand-inducible expression of transgenes in the mammary gland [Abstract]
Generation of a novel mouse strain that permits a temporally and spatially controlled expression of responder genes in embryonic and multiple adult tissues [Abstract]
Broad targeting of cyclin D functions may be essential for the effective treatment of ErbB2-induced breast cancers due to functional cross-compensation between cyclin D isoforms. [Abstract]
Generation of a novel transgenic mouse strain (MMTV-tTA) for the targeted expression of genes in the embryonic and postnatal mammary gland [Abstract].
A novel mouse model reveals essential roles for deregulated c-Myc in the initiation, progression, maintenance, and recurrence of pancreatic ductal adenocarcinoma [Abstract]. See also related article from 2014 on cancer cell dormancy in novel mouse models for reversible pancreatic cancer: a lingering challenge in the development of targeted therapies [Abstract].
The transcription factor Stat5 regulates the PI3-kinase/Akt1 pathway during mammary gland development and tumorigenesis [Abstract]. See also related article on novel transcripts from a distinct promoter that encodes the full-length AKT1 in human breast cancer cells [Abstract].
JAK1 conditional knockout, this member of the Janus kinase family seems to control the majority of STAT proteins that are active in the mammary gland, in particular STAT3, which is required for normal mammary gland remodeling [Abstract]
Pancreatic cancer cell dormancy; IGF1 signaling mediates residual disease in the absence of mutant KRAS or c-MYC as oncogenic drivers [Abstract ]
The Janus kinase 1 (JAK1) is an essential signaling node for inflammatory cytokine signals that mediate mammary cancer metastasis.
Highly metastatic claudin-low mammary cancers can originate from luminal epithelial cells, and our team participated in the development of the NSG-Pro mouse model that greatly improves the generation of patient-derived xenograft of human luminal breast cancers.
Special recognition of our work in scientific journals, web sites, newspapers, and radio
Our publication in Cancer Research by Lin et al. "Dormant cancer cells contribute to residual disease in a mouse model for reversible pancreatic cancer" was recommended in April of 2013 in F1000Prime.
“UNMC breast cancer researcher pushes science forward with his research”, interview with KIOS 91.5FM, February 20, 2012
“Dr. Wagner-led study yields novel breast cancer finding” UNMC News, January 24, 2012
“Cyclin D3 compensates for the loss of Cyclin D1 during ErbB2-induced mammary tumor initiation and progression.”MMHCC Newsletter, December 2011
This publication has been selected and evaluated by J Alan Diehl, a Member of the Faculty of 1000 (F1000), which places this work in F1000 library of the top 2% of published articles in biology and medicine.
“New ‘Knock-Out’ Gene Model Provides Molecular Clues to Breast Cancer” MMHCC Newsletter, October 2007
"Mammary Gland Cells Formed During Maternity Have Stem Cell Properties" NCI News Release, Dec. 6, 2004 [PDF]
"Parity-induced mammary epithelial cells promote tumor growth in transgenic mice" Health & Medicine Week, November 22, 2004, page 142 (Health & Medicine Week and Cancer Weekly via NewsRx.com ) [HTML]
"TSG101: An Antiviral Target with a Murky Past" in The Scientist 18:24, Jan. 19, 2004 [PDF]
"A Pregnancy-Induced Stem Cell: Is it the clue to pregnancy's anti-cancer effects?" in the Press Book of the 42ND ANNUAL MEETING of THE AMERICAN SOCIETY FOR CELL BIOLOGY, December 14-18, 2002 [PDF]
"Refining Transgenic Mice: Emerging technologies allow researchers to make tissue- and developmental stage-specific knockouts" in The Scientist 16:34, Jun. 24, 2002 [HTML]
"NIH Animal Model Uncovers a Role of BRCA1-Associated Breast Tumor Formation" NIDDK News Release [HTML]
"Branching out with BRCA1" in Nature Genetics 22: 10, May 1,1999 [PDF]
"New Model for Hereditary Breast Cancer" in Science 284: 723-725, Issue of 30 Apr 1999 [HTML]
"Research Shows Role of a Gene In Breast Cancer" in The Wall Street Journal, 04/30/1999 [HTML]
"Gene May Hold Cancer Clues" in Newsday, 04/30/1999 ppA32 [HTML]
"Wie erblicher Brustkrebs entsteht (German)" in a Press Release of the German Research Foundation (DFG), 04/30/1999, and in Informationsdienst Wissenschaft, 04/30/1999 [HTML] [HTML2]
"The Origins Of Hereditary Breast Cancer - Studies With Knock-Out Mice Reveal Underlying Mechanisms" inEurekAlert!, 04/30/1999 [HTML]
"Offenbar wirkt das intakte Gen wie ein Tumorsuppressor-Gen: So trägt BRCA1 zum Entstehen von Brustkrebs bei (German)" in ÄrzteZeitung, 8.6.1999 [HTML]
"Oxytocin and Mammary Gland Development" Newsletter of the UK Genetical Society, No. 36, May 1998 [HTML]