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From Michael A. Linden, MD, PhD
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Contact Me
If you would like to contact me I can best be reached by e-mail.
My e-mail address is michael.a.linden@gmail.com.
Alternatively, you may contact me by phone at 206-406-6325 (cell).
As I am relocating to the University of Minnesota in August 2011, the telephone number will change in the next few months
About Me
Welcome to my e-portfolio. My name is Michael Linden, and I received my MD-PhD degrees (Medical Scientist Training Program) at the University of Minnesota. My PhD was earned in the Microbiology, Immunology, and Cancer Biology PhD Program. As a graduate student I was an experimental hematopathologist; my work helped develop a new mouse model of multiple myeloma (link to editorial comment). Upon graduation from medical school, I entered the combined Anatomic and Clinical Pathology Residency Training Program at the University of Washington in Seattle, which I completed in June 2010. I am board certified in Anatomic and Clinical Pathology. I am currently a Hematopathology fellow at the Univeristy of Washington, and I will complete my clinical training in June 2011. This portfolio serves as an electronic compendium of my training and accomplishments.
Please click on the following links to view electronic copies of my CV and business card.
Career Goals
I have accepted a position as a assistant professor at the University of Minnesota and will join the hematopathology service, under the direction of Robert McKenna, MD. Initially I will attend on the morphology and flow cytometry diagnostic services in addition to developing a focused area of creative scholarship. As I have had considerable training in special coagulation testing and non-neoplastic hematology, I hope to be able to nurture some of these skills as a junior faculty member.
Highlighted Clinical Experiences
Overview
During my AP/CP training I had broad exposure to both anatomic and clinical pathology disciplines. The 29 months I spent in Anatomic Pathology taught me fundamental histology and cytology diagnostic skills that will enhance my ability to be a diagnostic hematopathologist. In addition to training in Hematopathology, my time in Clinical Pathology gave me considerable exposure to Immunology and Coagulation. Our Clinical Pathology training program is structured such that we gain considerable experience as Acting Lab Directors; these opportunities have given me the experience and skills to be an effective Assitant Lab Director at my next position.
Hematopathology
I am currently a hematopathology fellow. In addition to spending 12 months as fellow, I spent 9 weeks on the service during Clinical Pathology training. The University of Washington Hematopathology service provides diverse training opportunities for me. Our training includes:
General Hematology The hematology labs at UWMC and Harborview Medical Center use Sysmex automated hematology systems to count red cells, platelets, and white cells. Attending weekly Hematology Lab meetings have given me the opportunity to understand the nuances of automation.
Hematopathology - morphological evaluation of peripheral blood, body fluid, bone marrow, lymphoid tissue, and other anatomical locations involved by hematopoietic cell populations
Flow Cytometry- During my fellowship year I will spend 10 dedicated weeks learning how to extrapolate raw data collected into flow cytometry diagnostic reports. The Hematopathology Flow Cytometry Lab performs elaborate multi-color flow cytometry, as pioneered by Brent Wood, MD, PhD and other faculty.
Red cell disorders - evaluate red cell indices, iron studies, electrophoresis, HPLC, billiant cresyl blue staining, etc., to diagnose patients with thalassemias and hemoglobinopathies; flow cytometry based diagnosis of hereditary spherocytosis
Molecular diagnostics - B and T cell clonality gene rearrangment studies, PCR assays for t(11;14) and t(14;18) translocations, and screens for mutations in JAK2 V617F, FLT3 (currently offline), NPM1, and CEBP-Alpha.
Pediatric hematology - I will spend four weeks at Seattle Children's Hospital with their hematopathologist and see a wide variety of pediatric hematology cases, including bone marrow and other samples from children who have undergone stem cell transplantation
Reports
These are examples of some reports that I've generated in my training in Hematopathology
Hemoglobin Electrophoresis Report
Immunology
During my training I spent a total of 16 weeks in the Clinical Immunology Lab, including time spent as an Acting Director. I had the opportunity to become competent at the interpretation of serum and urine protein electrophoresis and immunofixation, oligoclonal banding pattern analysis of CSF samples, and CSF transferrin assays. I was also exposed to a variety of indirect immunoflluorescent assays and enzyme linked immunosorbent assays (ELISA). As an Acting Director, I was given graded responsibility to sign out the protein electrophoresis cases, all of which require physician interpretation at UWMC. By the end of the rotation, I was signing out 30-60 cases a day on my own, many with complexity due to changes related to stem cell transplantation. Additionally, I completed two research/method development projects which are outlined below in the Research section or in my CV.
Coagulation
During my training I will spent a total of 28 weeks in the Special Coagulation Labs, including time spent as an Acting Director. This experience helped me to gain confidence in a difficult discipline, and I participated in sign-out of twice weekly special coagulation cases, including venous thrombosis panels, factor inhibitor assays, and Von Willebrand Disease panels. Additionally, when opportunities arose, I was involved in the interpretation of 1:1 mixes and platelet aggregometry studies. Examples of some of these cases are listed below.
Heparin-induced Thrombocytopenia
Chemistry
My eight week chemistry rotation was spent at the Puget Sound Veterans Administration (VA) Hospital in Seattle. As I have interest and expertise in hematology and immunology, I spent time on this rotation validating immunoassays for the quantitation of serum immunoglobulins IgG, IgA, and IgM - these assays were previously not performed in-house. The VA hospital serves a large number of patients and has a significant hematology, oncology, and bone marrow transplant program - it was helpful to bring these tests online to decrease turnaround time and improve patient care. The validation studies involved comparing the results of immunoglobulin concentrations of 48 patients as measured on the Roche Cobas automated instrument (by an immunoturbidimetric method) to measurements made on a Dade Berhing nephelometer at the University of Washington Medical Center. I performed precision and method comparison studies as well as wrote procedures for all three tests, which are now on-line for clinical testing. Examples of the analyses and procedure for IgA can be found below:
Another quality improvement project I did while at the VA lead to discontinuation of superfluous testing. Operating room physicians had been asking for duplicate measurements of hematocrit - spun hematocrit and hematocrit by co-oximetry (as measured on a blood gas analyzer). The duplicate testing created extra work for the technologist on the blood gas bench, and the additional information gained was not additionally helpful. Thus, I helped to construct a memo to let the ordering physicians know that the spun hematocrit will not be performed routinely in the Chemistry Lab. A copy of this memo can be found below.
Discontinuation of Spun Hematocrit
Research
A more extensive enumeration of my research activities can be found on my CV above. These are additional examples not included elsewhere.
1) Cardiac autoantibodies and post-smallpox vaccination myocarditis. The Department of Defense (DoD) has immunized over 1,000,000 individuals with the smallpox vaccine since the threat of bioterrorism resurfaced in 2001. While relatively safe, a subset of vaccinees develop myocardititis. Researchers at UWMC and the DoD are collaboratively working to understand the genetic and immunologic relationships between smallpox vaccination and myocarditis. We received sera from this trial to evaluate for humoral markers of myocarditis. I set up heart and skeletal muscle indirect immunofluorescence assays and evaluated for these markers in two groups of vaccinees - those with and without clinical myocarditis. Interestingly, the vaccinees with myocarditis were less likely to have anti-sarcolemmal antibodies in their sera. Our collaborators are now trying to understand if the genetic differences among the groups may account for immunologic differences. While my contribution to the project is complete, our collaborators' studies are ongoing.
2) Circulating microparticles in trauma patients. Currently, I am working on research in the coagulation laboratory under the guidance of Wayne Chandler, MD to better understand the acute coagulopathy of trauma (ACT). Some trauma patients enter the emergency department with an apparently normal prothrombin time (PT), only to develop ACT hours later. Prior observations have noted that trauma patients that develop ACT are more likely to have elevated circulating tissue factor (TF); independently, ACT patients have elevated thrombin generation. We hypothesize that TF-bearing microparticles enter circulation after major trauma and that increased concentration is predictive of ACT. The microparticles are too small to be seen by conventional microscopy, and a majority of them are too small to be resolved by flow cytometry. Thus, I’m using procoagulant clot and thrombin generation assays, with and without an inhibitory anti-TF antibody, to determine the role of circulating TF. Interestingly, while some ACT patients have elevated procoagulant activity and thrombin generation due to TF, they don’t always correlate. I am now trying to develop an assay to measure Factor XIa (FXIa) in addition to TF, as we think that circulating FXIa may be an additional procoagulant in our patient samples. The long term goal of this project is to create new diagnostic tests that will be useful for our trauma center to predict which patients will develop major coagulopathy, despite having entered the hospital with a normal PT.
Education/Service
A more extensive enumeration of my educational and service activities can be found on my CV above. I have highlighted a few examples here.
1) Editorial Internship Last year, the Chair of Pathology nominated me for the position of editorial intern at the journal of Laboratory Investigation. The editors of this journal are aware of the fact that graduate students, post-docs, residents, fellows, and junior faculty receive little or no formal training in the review of manuscripts before papers to referee just start appearing in their inboxes. Thus, the journal has created an opportunity to act as reviewers for manuscripts in a mentored environment. I have had the opportunity to be the third reviewer of multiple manuscripts, and my reviews have all been communicated blindly to the authors, ultimately influencing the manuscript publication decision.
2) Peer Consultation My peers often turn to me for help with written communication. As an MSTP student, I would often help undergraduate students edit their application essays to medical, graduate, and professional schools. Now that I am a fellow, I often provide this consultation to my peers. I have had the opportunity to help them shape their personal statements, grant applications, meeting abstracts, etc. A summary of some of these consultations appears in the table linked below. These skills will be a valuable asset in an academic career in which I hope to mentor and advise trainees.