The Laboratory-based Physician Scientist

The Laboratory-based Physician Scientist

Michael Carrithers, MD, PhD Director, Program in Neuroimmunology and Neurological Infections Associate Professor Departments of Neurology and Microbiology & Immunology University of Illinois-Chicago Jesse Brown VA Hospital

Overview A bit of science Life and career path Bit more science The sandwich and land of cheese The lean model of an academic laboratory Career development

Carrithers Laboratory Novel adaptive and innate immune signaling mechanisms in viral and autoimmune disease of the CNS Genetic determinants of response to a MS treatment Role of macrophages in recovery from inflammatory injury Novel viral pattern recognition mediated by intracelllular sodium channels Disclosures: Biogen-Idec/Elan

The SCN5A pathway regulates transcriptional response to cytosolic poly I:C, a mimic of viral dsrna

Cytosolic poly I:C increases the macrophage SCN5A inward current and decreases the outward current

Current work The Aedes aegypti AAEL006019 sodium channel variant is a pattern recognition molecule for ssrna. Co-evolution of virus, vector and host autoimmunity. Signaling by human macrophage SCN5A and other pattern recognition channels: Anti-viral immunity and autoimmunity Transcription and cytoplasmic RNA splicing Regulation of secretome (immune responses and axonal growth)

Life Path

Medical Scholars 1984-1992: Challenges Length of time for graduate work Potential thesis topics tended not to be diseasebased Few (or no) physician scientists No university hospital M3-M4 clinical training and evaluation Distant, non-academic VA Absence of academic clinical chairs Rationale for picking area for residency

Yale University and Yale New-Haven Hospital Neurology residency (research track) Marriage Chief Resident in Neurology Fellowship in basic immunology and clinical neuroimmunology/multiple sclerosis Parenthood Junior faculty Independent laboratory

Original goal was to determine how normal CNS immune surveillance occurred

CNS immune surveillance occurs predominantly through the blood-csf barrier

CNS immune surveillance by T lymphocytes is not dependent on alpha 4 integrin

Regulation of clinical responsiveness to antialpha 4 integrin treatment in experimental autoimmune encephalomyelitis (EAE) by epithelial V-like antigen (EVA)

The increased humoral response in EVA-KO occurs systemically and in the CNS

Expectation of work-life balance can be wrong

The Lean Laboratory Model

Current clinical and teaching activities Weekly half day subspecialty MS clinics at UIC and JBVA 8 weeks of inpatient coverage Resident and student teaching Program development Administrative Physician scientist and access to graduate students

The Lean Laboratory Model: Lab Management

The Lean Laboratory Model: Resource Allocation In lab: Tissue culture, microscopy for histology and live cell imaging, qpcr, electrophysiology Local core facilities: Genomics, flow cytometry, animal care Off-site: Proteomics, transgenic mouse breeding and genotyping Limited staff Vastly improved bench techniques over last 20-25 years

Career development in academic medicine

Faculty tracks Traditional tenure track Clinician scientist Clinician educator

When does promotion clock start? Know specific requirements for your track. Mentor committees can be helpful or can hinder progress. Usually need expertise in a subspecialty or specific area of interest (generalists) Research publications, grants, clinical trials, reviews, case studies, local and national talks, teaching, administrative duties

UIC Neurology New chair (Jeff Loeb, MD, PhD) Five new physician scientist hires in MS, neurooncology, stroke, neuromuscular, and epilepsy Clerkship available

Questions