Jump Starting My Research Career. Shannon L. Meeks, MD March 7, 2018

Transcription

1 Jump Starting My Research Career Shannon L. Meeks, MD March 7,

2 Disclosures Advisory committees: CSL Behring, Bayer, Shire, Genentech, Bioverativ, HEMA Biologics and Grifols Research Support: Pfizer, NHF, HTRS, NIH

3 Hemophilia: Early Observations For it was taught: If she circumcised her first child and he died [as a result of bleeding from the operation] and a second one died [similarly], she must not circumcise her third child. R. Judah, the Patriarch, redactor of the Mishnah Rosner F. Medicine in the Bible and the Talmud, revised ed, New York: Yeshiva University Press, Ktav Publishing House, 1995.

4 My Path: Early Observations from a Summer Job I ve been debating about teaching math and coaching or going to med school but I think I really like what is happening here at the Mississippi Children s Cancer Clinic especially the bleeding and clotting which is like solving a puzzle. ~Summer of 94

5 Education BS Mathematics at Duke University Medical School at the University of Mississippi Pediatrics at the University of Virginia Pediatric Hematology/Oncology at Emory University Chosen primarily because of strength in hemostasis Career plan: general hem/onc physician at small program with focus on hemophilia

6 Fellowship Research Options Clinical I was a math major Stats/epi come easy I ve never pipetted Dr. Pete Lollar Basic Importance of coagulation testing to clinical care Dr. Abshire You ll never regret having spent time in the lab with a world renown factor VIII expert

7 This Case Sold Me.. MD came as one of my first continuity patients at the age of 4 after she presented to hospital with new onset seizure and subdural hematoma Diagnosed with SCIDS and had BMT in first year of life with no chronic GVHD Laboratory evaluation PT/PTT: 9.2/72.2 PTT did not correct with hepzyme Mixing study PTT 66.9 Lupus Profile-WNL

8 Further evaluation Mixing studies did not correct the PTT Factor VIII level <1% Human Factor VIII inhibitor BU Porcine Factor VIII inhibitor- >256 BU Diagnosis= acquired hemophilia

9 Further evaluation After IRB approval and consent of family peripheral blood was drawn from patient and her bone marrow donor. What are the properties of the inhibitor? To what portion of the fviii molecule is it directed? Multiple domain specificities including C2 epitope Inhibited her donor s fviii as well Nicely overlapped with a project that Pete Lollar had just finished which involved making murine anti-human fviii MAbs I began with characterizing the C2 domain antibodies to attempt to better characterize this patient s antibodies

10 Another Clinical Question: Why do a subset of patients with titers >10 BU/ml respond to high dose fviii while others with lower titers do not. IB001A: 22 BU/ml IB008H: 29 BU/ml 10

11 Another Clinical Question: Why do a subset of patients with titers >10 BU/ml respond to high dose fviii while others with lower titers do not. NOTHING WORKS AS WELL AS FVIII!! High-dose fviii Recombinant porcine fviii* What is different about the antibodies in patients with high inhibitor titers that respond to treatment with fviii and those that do not respond?

12 Take Home Messages from My Early Path It was imperative that I find a research path that allowed me to address critical questions that I saw in my patients I needed a lab that understood that I had a lot of hemophilia knowledge but no laboratory skills The purely basic science elements were Pete s but early on I was given the space to develop the translational questions and the tools to answer them 12

13 A Research Career Doesn t Happen Overnight: Take Advantage of Funding Opportunities 2 years of fellowship research (NHF Clinical Fellowship) 2 years post-doctoral training while a clinical instructor HTRS early career award Remember you are competing with others that might have a lot more previous research experience Need LOTS of protection of your time Started to find my niche Assistant Professor K08 vs. K23 Still need LOTS of protection of your time Transition to independent investigator

14 Associate Professor Basic/translational laboratory R01, U54, HTRS, NHF funding All include clinical samples Where I am now Most basic researcher on a number of clinical projects/committees and most clinical on a number of science projects/committees

15 Where I am now The translational piece is where my passion lies Having novel translational ideas and laboratory skills has allowed me to become significantly more involved in clinical projects (HIPS, Expression Therapeutics) Understanding basic laboratory research has allowed me to be the clinical/translational piece of studies for 5 different investigators (gene therapy, GpIb/VWF biology, protein evolution, biomechanical engineering, immunology)

16 Challenges of Jump Starting a Research Career Picking a research focus Identify your resources and your skill deficits May have to choose between your favorite topic and the best fit for training given your needs and the institutional resources Getting and maintaining funding For clinical researchers often requires piecing together funding from multiple smaller grants Finding a niche that is different from your mentor How to transition your continued training to your first faculty position

17 Things to Consider as You Jump Start Your Career Identify non-institutional resources ASH CSTI Get involved Make connections with others in your field Hemostasis/Thrombosis is a relatively small field Given small patient numbers in some diseases you need collaborators Be willing to consider other plans/focuses 1 7

18 Things to Consider as You Jump Start Your Career 1 8

19 Questions? BC AB B A 19