William G. Schuett, Jr., Multiple Myeloma Research Laboratory
Our primary research interest concerns multiple myeloma, a neoplasm of terminally differentiated, immunoglobulin-producing B lymphocytes that reside in the hematopoietic bone marrow and are called plasma cells. We use genetically engineered mouse models of human myeloma as the principal experimental model system to elucidate mechanisms of malignant plasma cell development and evaluate new approaches to myeloma treatment and prevention. Working in close association with our clinical colleagues in the Division of Hematology and Oncology, we employ a bench-to-bedside-and-back strategy to translate laboratory advances to curing myeloma.
The laboratory is generously supported by an endowment in memory of William G. Schuett, Jr., a cancer advocate and business leader who lost his battle with myeloma after a long, heroic fight. The laboratory was established in 2018 and is directed by Dr. Siegfried Janz, the inaugural William G. Schuett, Jr., Multiple Myeloma Endowed Chair.
About the PI
After obtaining his medical degree and board certification in Clinical Immunology from the University of Leipzig, Germany, Siegfried Janz joined the Laboratory of Genetics at the National Cancer Institute (NCI), Bethesda, Maryland. He performed studies on the inflammation-dependent peritoneal plasmacytoma, the first-generation mouse model of human plasma cell neoplasms such as multiple myeloma, plasmacytoma and plasma cell leukemia. His tenure at NCI shaped an enduring fascination with fundamental and translational research into plasma cell malignancies.
In 2007 Janz joined the Department of Pathology at the University of Iowa (UI) Roy J. and Lucille A. Carver College of Medicine as a full research professor to conduct studies on second-generation mouse models of human myeloma dependent on deregulated expression of the cellular oncogene MYC (c-myc). This work took advantage of gene-insertion mice generated in the Janz Lab to mimic different fine structures of the human MYC-activating t(8;14)(q24;q32) translocation. As leader of the cancer genetics program, he was actively engaged in research efforts at the UI Holden Comprehensive Cancer Center.
In 2018 Janz relocated his laboratory to the Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin (MCW) Milwaukee, where he joined the Clinical Cancer Center and its Developmental Therapeutics Program. Janz currently works on an NCI-supported project (2R01CA151354), entitled “Biological validation of candidate myeloma genes,” that seeks to elucidate genetic pathways underlying malignant plasma cell transformation. Additionally, he serves as a subcontractor on a NCI project (1R01CA214246) directed by Dr. Alan Lichtenstein, UCLA, concerned with the mechanism by which the ribonucleoprotein hnRNP A1 regulates the translation of MYC message in myeloma cells.
Fumou Sun, MS
Education: China Pharmaceutical University, PhD Microbial and Biochemical Pharmacy
Research: My MS and PhD training (defense scheduled 06/2019) were in the area of antibody engineering. I generated humanized and genetically engineered bispecific antibodies. Beginning in 2017, I have been developing expertise in multiple myeloma first at the University of Iowa and currently the Medical College of Wisconsin. Currently, I am carrying out studies on osteolytic lesions resembling human myeloma bone disease in transgenic mice. This project utilizes integrated 3D X-ray microscopy and µCT analysis to assess, for the first time, bone loss in plasma cell tumor-bearing mice in an objective, unbiased manner. I am also involved in ongoing studies on the biological validation of candidate myeloma drivers such as forkhead box M1 transcription factor, FOXM1.
Michael Pisano, BS
Education: Truman State University, BS Biology
Research: During my time in undergrad I learned basic RNA sequencing analysis in R language, worked on an epitope mapping project at A. T. Still University, and contributed to assay development as an R&D intern at Thermo Fisher Scientific, Carlsbad, CA. I joined the Janz lab at the University of Iowa as an Immunology graduate student in June 2017 and relocated in Fall 2018 to MCW where I hold a research appointment. My current project concerns genomic analysis of myeloma-like plasma cell tumors in a double-transgenic mouse model of human myeloma. To that end, I rely on next generation DNA and RNA sequencing, and proteomics. Of importance to my PhD dissertation project, I perform immunological studies including analysis of bone marrow infiltrating Th17 cells which have been implicated in myeloma bone disease.
Krista Lingle Mullen, BS
Education: Eastern New Mexico University, BS Anthropology, BS Forensic Science
Research: I joined the Janz lab as a MS student of pathology at the University of Iowa in Spring 2017. My thesis project is focused on genetic targeting of the transcription factor FOXM1 using CRISPR/Cas9 genome editing tools. The principle goal is to delete FOXM1 function in myeloma cell lines to elucidate pathways of FOXM1 dependent growth and survival. This will facilitate development of new FOXM1 targeted therapies for the treatment of high-risk multiple myeloma.
Yan Cheng, MS
Education: China Pharmaceutical University, MS Pharmacokinetics
Research: My PhD project in China (defense scheduled 06/2019) concerns the impact of psychological depression on prostate cancer progression. I found that sympathetic nerve activated FAK (focal adhesion kinase) in prostate cancer cells resulted in increased cancer invasion and tumor matrix remodeling. Also, I demonstrated that sympathetic activation induced neuropeptide Y (NPY) expression in prostate cancer cells attracted myeloid cell (Mo-MDSCs and macrophages) infiltration in the tumor and stimulated IL-6/STAT3 signaling in cancer cells. In April 2018 I joined the Janz Lab where I am currently using adoptive B cell transfer in the double transgenic IL6Myc mouse model of human myeloma to elucidate biological pathways of neoplastic plasma cell development. Besides FOXM1, this involves candidate genes identified in Michael’s genomic analysis described above. Additionally, I am developing projects studying the role of sympathetic nerve system and neural factors in multiple myeloma-a flagrantly understudied area of blood cancer research.
Validation of forkhead box M1 (FOXM1) as a new therapeutic target in high-risk myeloma
Regulation of c-Myc proto-oncogene (MYC) translation by heterogeneous nuclear ribonucleoprotein A1 (HNRPA1)
William G. Schuett, Jr., Multiple Myeloma Research Laboratory