Michael Linden, M.D., Ph.D.

Associate Professor, Department of Laboratory Medicine and Pathology

Michael Linden

Contact Info

linde013@umn.edu

Office Phone 612-624-8446

Lab Phone 612-273-5136

Mailing Address:
MMC 609 Mayo
420 Delaware St SE
Minneapolis, MN 55455

Associate Professor, Department of Laboratory Medicine and Pathology


Pathologist


MD, MD, PhD University of Minnesota (Medical Scientist Training Program), 2006

University of Washington, Seattle (Anatomic and Clinical Pathology), 2006-2010

University of Washington, Seattle (Hematopathology), 2010-2011

Saint Mary's University, Winona, MN (Biology), 1998

Summary

Awards & Recognition

  • CTSI Office of Discovery and Translation Grant Recipient (Principal investigator), 2013
  • MCC Hematologic Malignancy Innovations Award (Co-Investigator), 2013
  • Resident Distinguished Teaching Award in Clinical Pathology, 2012
  • Institute of Human Genetics Seed Grant Recipient (Co-Investigator), 2012
  • Certificate of Excellence (top 5% of all reviewers for Laboratory Investigation), 2011
  • J. Jacob Kaplan Research Award, 2006
  • J. Thomas Livermore Research Award, 2004
  • University of Minnesota Medical School Advanced Admissions Program Acceptance, 1996
  • CRC Press Freshman Chemistry Award, 1995

Professional Associations

  • Academy of Clinical Laboratory Physicians and Scientists (ACLPS)
    • Program and Finance Committee, 2013-Present
  • American Society for Clinical Pathology (ASCP)
  • American Society of Hematology (ASH)
  • College of American Pathologists (CAP)
    • Diagnostic Immunology Resource Committee, 2013-Present
    • Standards Committee, Appointed for 2014
  • Society for Hematopathology and European Association for Hematopathology (SH-EAHP)
  • United States and Canadian Academy of Pathology (USCAP)

Research

Research Summary/Interests

Dr. Linden is Director of Hematopathology. As a graduate student, he developed a novel genetically engineered mouse model of multiple myeloma with characteristics similar to those found in human disease. Linden has continued doing research on multiple myeloma and other plasma cell neoplasms while translating that knowledge to clinical application through improved laboratory diagnoses, clinical monitoring, and prediction of disease resistance to therapy.

Multiple myeloma is characterized by the proliferation of malignant plasma cells within the bone marrow. Compared to other lymphoid malignancies, the disease has been difficult to study and treat due to its genetic heterogeneity. Investigators use murine and human myeloma cell lines, xenograft models, and genetically engineered mice to identify the multiple genetic pathways involved in the pathobiology of the disease as well as mechanisms of drug resistance. Linden is collaborating with colleagues who are using murine and human cell lines, in addition to primary human samples, to characterize genotypic and immunophenotypic signatures of drug resistance.

Linden’s laboratory is working to create new diagnostic tests that will aid in predicting chemotherapeutic sensitivity or disease resistance—an individualized therapy approach. In addition, as the analytic sensitivity of flow cytometric methods to evaluate for minimal residual disease is improving, Linden is working with the College of American Pathologists (CAP) to improve and standardize diagnostic testing.

In recent years the treatment approach to multiple myeloma has been the subject of a “cure versus control” discussion among clinicians. As novel chemotherapeutic combinations and transplant continue to improve treatment, the likelihood of cure continually increases. Simultaneously, clinical teams have asked for improved diagnostic testing to help define cure. Linden hopes to use his role as a CAP committee member to guide efforts to improve standardization and quality of flow cytometric testing for myeloma patients.

Publications

Selected Invited Lectures

  • "Integrated laboratory diagnosis of plasma cell neoplasms – a morphologic, genetic, and flow cytometric approach." American Society of Clinical Pathology national meetings, Boston, MA and Chicago, IL - 2012, 2013
  • "Immunophenotypic features of bortezomib-resistant plasma cells toward personalized therapy in plasma cell myeloma." Saint Mary’s University, Department of Biology, Bioseminar, Winona, MN - 2013
  • "Laboratory diagnosis of plasma cell neoplasms." East Metro Multiple Myeloma Patient Support Group, Stillwater, MN - 2012
  • "Laboratory diagnosis of plasma cell dyscrasias and paraproteinemia associated disorders." Vanderbilt University Medical Center, Department of Pathology, Special Seminar, Nashville, TN - 2011
  • "Laboratory diagnosis of plasma cell dyscrasias and paraproteinemia associated disorders." University of California-Davis Department of Pathology and Laboratory Medicine Grand Rounds, Sacramento, CA - 2010

Selected Publications

  • Ustun, C., Courville, E. L., DeFor, T., Dolan, M., Randall, N., Yohe, S., Bejanyan, N., Warlick, E., Brunstein, C., Weisdorf, D. J., Linden, M. A. Myeloablative, but not Reduced-Intensity, Conditioning Overcomes the Negative Effect of Flow-Cytometric Evidence of Leukemia in Acute Myeloid Leukemia. Biology of Blood and Marrow Transplantation. 2016; 22(4):669-675.
  • Courville EL*, Singh C*, Yohe S, Linden MA, Naemi K, Berger M, Ustun C, McKenna R, Dolan M. Patients with a history of prior chemotherapy and isolated del(20q) with minimal myelodysplasia have an indolent course. *co-first authors. Am J Clinical Pathol.2016 Apr; 145(4):459-66.
  • Keeney, M., Halley, J. G., Rhoads, D. D., Ansari, M. Q., Kussick, S. J., Kussick, S. J., Karlon, W.J., Mehta, K. U., Dorfman, D. M., Linden, M. A. Marked variability in reported minimal residual disease lower level of detection of 4 hematolymphoid neoplasms a survey of participants in the
    college of American pathologists flow cytometry proficiency testing program. Archives of Pathology and Laboratory Medicine. 2015; 139(10):1276-1280.
  • Linden, M. A., Sedgewick, G. J., Ericson, M. An Innovative Method for Obtaining Consistent Images and Quantification of Histochemically Stained Specimens. Journal of Histochemistry andCytochemistry. 2015; 63(4):233-243.
  • Mao, Z. J., Surowiecka, M., Linden, M. A., Singleton, T. P. Abnormal immunophenotype of the T-Cell-Receptor beta chain in follicular-helper T Cells of angioimmunoblastic T-cell lymphoma.. Cytometry. Part B, Clinical cytometry. 2015. In press.
  • Fall, D. J., Stessman, H., Patel, S. S., Sachs, Z., Van Ness, B. G., Baughn, L. B., Linden, M. A. Utilization of translational bioinformatics to identify novel biomarkers of bortezomib resistance in multiple myeloma.. Journal of Cancer. 2014; 5(9):720-7.
  • Magnusson, E., Cao, Q., Linden, M. A., Frolich, J. W., Anand, V., Burns, L. J., Bachanova, V. Hematopoietic cell transplantation for mantle cell lymphoma: Predictive value of pretransplant positron emission tomography/computed tomography and bone marrow evaluations for outcomes. Clinical Lymphoma, Myeloma and Leukemia. 2014; 14(2):114-121.
  • Dayton, V. J., Fink, J. M., Linden, M. A., McKenna, R. W., Yohe, S. L., Park, K., Kubic, V. L. Quality and adequacy of bone marrow samples obtained by the 2-needle technique: The Minnesota experience. Archives of Pathology and Laboratory Medicine. 2014; 138(7):860-862.
  • Stessman, H. A. F., Mansoor, A., Linden, M. A., Van Ness, B. V., Baughn, L. B. Stabilization of activation induced cytidine deaminase by bortezomib does not confer increased drug target mutation frequency. Leukemia and Lymphoma. 2014; 55(1):220-222.
  • Stessman, H. A. F., Mansoor, A., Zhan, F., Linden, M. A., Van Ness, B. V., Baughn, L. B. Bortezomib resistance can be reversed by induced expression of plasma cell maturation markers in a mouse in vitro model of multiple myeloma.. PloS one. 2013; 8(10).
  • Üstün, C., Wiseman, A. C., Defor, T. E., Yohe, S. L., Linden, M. A., Oran, B. M., Burke, M. J., Warlick, E. D., Miller, J. S., Weisdorf, D. J. Achieving stringent CR is essential before reduced-intensity conditioning allogeneic hematopoietic cell transplantation in AML. Bone Marrow Transplantation. 2013; 48(11):1415-1420.
  • Stessman, H. A. F., Mansoor, A., Zhan, F., Janz, S., Linden, M. A., Baughn, L. B., Van Ness, B. V. Reduced CXCR4 expression is associated with extramedullary disease in a mouse model of myeloma and predicts poor survival in multiple myeloma patients treated with bortezomib. Leukemia. 2013; 27(10):2075-2077.
  • Burke, M. J., Burns, L. J., Linden, M. A., Lindgren, B. R., Verneris, M. R., Weisdorf, D. J., Üstün, C. How do we define complete remission for acute myeloid leukemia in the current era? Results of an international survey. American Journal of Hematology. 2013; 88(9):826-827.
  • Conway, A. B., Kaufman, S. C., Rudrapatna, V. K., Linden, M. A. Crystallizing
    immunoglobulin presenting as polychromatic crystalline keratopathy: An unusual clinical presentation of monoclonal gammopathy of undetermined significance (MGUS). Laboratory Medicine. 2013; 44(4):344-347.
  • Stessman, H. A. F., Baughn, L. B., Sarver, A. L., Xia, T., Deshpande, R., Mansoor, A., Walsh, S. A., Sunderland, J. J., Dolloff, N. G., Linden, M. A., Zhan, F., Janz, S., Myers, C. L., Van Ness, B. V. Profiling bortezomib resistance identifies secondary therapies in a mouse myeloma model. Molecular Cancer Therapeutics. 2013; 12(6):1140-1150.
  • Singh, C., Yohe, S., Baughn, L., and Linden, M.A. Utility of flow cytometry to classify abnormal plasma cell populations in marrow samples collected from patients with putative plasma cell neoplasms. Open journal of blood diseases. 2012 Sep; 2(3): 39-45.
  • Linden, M. A., Kirchhof, N. A., Carlson, C. S., Van Ness, B. V. Targeted overexpression of an activated N-ras gene results in B-cell and plasma cell lymphoproliferation and cooperates with c-myc to induce fatal B-cell neoplasia. Experimental Hematology. 2012;

Clinical

Specialties

  • Neoplastic hematopathologyNon-neoplastic hematologyLeukemiaSpecial coagulation testingMultiple myelomaLymphoma 

Board Certifications

American Board of Pathology

  • Anatomic and Clinical Pathology
  • Hematology