George Earl Georges MD

Focus of Work:

The overarching goal of my translational research work is to improve the survival and quality of life for patients with severe autoimmune diseases using the highly effective therapies of hematopoietic stem cell transplantation, cellular therapy and immunotherapy.

Basic research:

The goal of the basic research program is to assess molecular and cellular mechanisms of immune dysfunction caused by autoimmune disease. This is evaluated in patients prior to hematopoietic stem cell transplantation (HSCT), cellular therapy (chimeric antigen receptor-T cell [CAR-T]), or other novel immune cellular treatments. In addition, we assess the mechanisms of immune reconstitution after HSCT/ CAR-T/ immunotherapy. The aim is to identify the key molecular and cellular drivers of immune regulation and investigate the mechanisms that achieve durable remission of disease in treated patients. Using patient’s research blood and tissue samples from before and after HSCT/ cellular therapy, we aim to identify the pathways by which HSCT/ cellular therapy re-establishes immune regulation using cutting-edge single cell RNA sequencing, proteomics, epigenetics and bioinformatics analysis.

Clinical Research:

Hematopoietic stem cell transplantation (HSCT): autologous or allogeneic HSCT for autoimmune diseases.  The field of HSCT has made enormous strides with dramatic improvement in safety and efficacy for patients with leukemia/ lymphoma/ blood cancers/ aplastic anemia over the past few decades. My aim is to bring these improved treatments to patients who have severe, disabling, life-threatening autoimmune diseases so that they may also benefit from these novel therapies. The goal is to provide safer, highly effective and potentially curative treatment to patients with autoimmune diseases instead of life-long chronic immunosuppression.   

Chimeric antigen receptor T cell (CAR-T) therapy is a new treatment that is currently US FDA-approved for the potentially curative treatment of lymphoma, multiple myeloma and acute lymphocytic leukemia. There is very recent evidence that CAR-T therapy may be highly effective for patients with autoimmune diseases. CAR-T works by targeting and eliminating abnormal B-cells and thereby resets the immune system in patients with autoimmune disease. I am highly focused on bringing this new treatment to patients with systemic lupus erythematosus, lupus nephritis, myositis, dermatomyositis, diffuse scleroderma, ANCA vasculitis and to patients with multiple sclerosis. We have opened several phase I/phase II trials evaluating CAR-T therapy. Additional cellular therapy trials are in development.  

Autoimmune diseases treated with HSCT and/ or CAR-T include:

Neurologic autoimmune diseases such as multiple sclerosis (MS) including relapsing remitting, secondary progressive and primary progressive MS, stiff person syndrome (SPS), myasthenia gravis, chronic inflammatory demyelinating polyneuropathy (CIDP), neuromyelitis optica (NMO), autoimmune encephalitis.

Rheumatologic diseases: systemic sclerosis (SSc, diffuse with interstitial lung disease), myositis, systemic lupus erythematosus (SLE), anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis.

Clinical Trials:

Progress in clinical outcomes for patients with severe autoimmune diseases is achieved through research involving HSCT and CAR-T clinical trials. Likewise, participation in clinical trials is how meaningful improvements in patient outcomes is achieved.  Dr. Georges is the Transplant Principal Investigator for the BEAT-MS study, a multi-center, randomized, clinical trial sponsored by the National Institutes of Health (NIH) and the Immune Tolerance Network (ITN). HSCT can also be performed as part of clinical care treatment plan (in which the patient’s insurance may cover the cost of treatment). CAR-T trials are conducted in partnership with pharmaceutical industry sponsors. The HSCT and CAR-T treatments at Northwestern University/ Northwestern Medicine for patients with autoimmune diseases are conducted under clinical trials directed by Dr. Georges.

Keywords: Autoimmune disease, Hematopoietic stem cell transplantation (HSCT), chimeric antigen receptor therapy (CAR-T), systemic sclerosis (scleroderma), multiple sclerosis (MS), systemic lupus erythematosus (SLE, lupus, lupus nephritis), myositis (dermatomyositis).

Education:

Bachelor of Science: Massachusetts Institute of Technology (1986)

Medical Doctor: University of California, San Francisco (1990)

Postgraduate Training:

Intern and Resident Internal Medicine: University of Texas, Southwestern (Parkland Memorial Hospital), Dallas, Texas (1990-93)

Fellowship: Medical Oncology, Fred Hutchinson Cancer Research Center, University of Washington Seattle, Washington (1994-97)

Certification:

Diplomate, Medical Oncology, American Board of Internal Medicine (ABIM)

Current Faculty Position:

Professor of Medicine, Department of Hematology/Oncology,

Director of Hematopoietic Stem Cell Transplant/ Cellular Therapy Program for Autoimmune Diseases,

Northwestern University Feinberg School of Medicine, Chicago, IL

Recent Publications (selected from over 90 manuscripts/ chapters):

Georges GE, Khanna D, Wener MH, Mei MG, Mayes MD, Simms RW, Sanchorawala V, Hosing C, Kafaja S, Pawarode A, Holmberg LA, Kolfenbach J, Furst DE, Sullivan KM, Huang S, Gooley T, Nash RA. Autologous non-myeloablative hematopoietic stem cell transplantation for diffuse cutaneous systemic sclerosis: identifying disease risk factors for toxicity and long-term outcomes in a prospective, single-arm trial. Arthritis and Rheumatology, 2024 Dec 3. doi: 10.1002/art.43072. Online ahead of print. PMID: 39624016

McDonald GB, Landsverk OJB, McGovern DPB, Aasebo A, Paulsen V, Haritunians T, Reims HM, McLaughlin BM, Zisman T, Li D, Elholm ETMM, Jahnsen FL, Georges GE, Gedde-Dahl T. Allogeneic bone marrow transplantation for patients with treatment-refractory Crohn’s Disease. Heliyon. 2024 Jan 3, doi: 10.1016/j.helioyon.2024.e24026. PMID: 38283244

Schlatter MI, Yandamuri SS, O’Connor KC, Nowak RJ, Pham MC, Obaid AH, Redman C. Provost M, McSweeney PA, Pearlman ML, Tees MT, Bowen JD, Nash RA, Georges GE. Remission of severe myasthenia gravis after autologous stem cell transplantation. Annals of Clinical and Translational Neurology. 2023 doi: 10.1002/acn3.51898. PMID: 37726935

Celli SI, Nash R, Money KM, Garza M, Borko TL, Mizenko C, McMenamin C, Von Geldern G, Georges G, Piquet AL. Successful autologous hematopoietic stem cell transplantation in glycine receptor antibody-positive stiff person syndrome: a case report. Neurol Neuroimmunol Neuroinflamm. 2024 Mar;11(2):e200197. doi: 10.1212/NXI.0000000000200197. PMID: 38170953

Georges GE, Bar M, Onstad L, Yi JC, Shadman M, Flowers ME, Carpenter PA, Stewart S, Lee SJ, Holmberg LA. Survivorship after Autologous Hematopoietic Cell Transplantation for Lymphoma and Multiple Myeloma: Late Effects and Quality of Life. Biol Blood Marrow Transplant. 2020 Feb; 26(2):407-412. doi: 10.1016/j.bbmt.2019.10.002. PMID:31605822.

Cohen JA, Baldassari LE, Atkins HL, Bowen JD, Bredeson C, Carpenter PA, Corboy JR, Freedman MS, Griffith LM, Lowsky R, Majhail NS, Muraro PA, Nash RA, Pasquini MC, Sarantopoulos S, Savani BN, Storek J, Sullivan KM, Georges GE. Autologous Hematopoietic Cell Transplantation for Treatment-Refractory Relapsing Multiple Sclerosis: Position Statement from the American Society for Blood and Marrow Transplantation Biology of Blood and Marrow Transplantation. Biol. Blood Marrow Transplant, 2019, May;25(5):845-854. doi: 10.1016/j.bbmt.2019.02.014. PMID:30794930

Georges, GE. Consider Allogeneic Bone Marrow Transplantation for Older, Fit Patients with Aplastic Anemia. Biol Blood Marrow Transplant, 2019 Mar; 25(3):e69-70. doi: 10.1016/j.bbmt.2019.01.015. PMID:30641134.

Sullivan KM, Majhail NS, Bredeson C, Carpenter PA, Chatterjee S, Crofford LJ, Georges GE, Nash RA, Pasquini MC, Sarantopoulos S, Storek J, Savani B, St Clair EW. Systemic Sclerosis as an Indication for Autologous Hematopoietic Cell Transplantation: Position Statement from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 24(10):1961-1964, 2018. PMID:29953945

Sullivan KM, Goldmuntz EA, Keyes-Elstein L, McSweeney PA, Pinckney A, Welch B, Mayes MD, Nash RA, Crofford LJ, Eggleston B, Castina S, Griffith LM, Goldstein JS, Wallace D, Craciunescu O, Khanna D, Folz RJ, Goldin J, St Clair EW, Seibold JR, Phillips K, Mineishi S, Simms RW, Ballen K, Wener MH, Georges GE, Heimfeld S, Hosing C, Forman S, Kafaja S, Silver RM, Griffing L, Storek J, LeClercq S, Brasington R, Csuka ME, Bredeson C, Keever-Taylor C, Domsic RT, Kahaleh MB, Medsger T, Furst DE; SCOT Study Investigators. Myeloablative Autologous Stem Cell Transplantation for Severe Scleroderma. N Engl J Med. 378(1):35-47, 2018. PMID:29298160.

Nash, R.A., Hutton, G.J., Racke, M.K., Popat, U., Devine, S.M., Steinmiller, K.C., Griffith, L.M., Muraro, P.A., Openshaw, H., Sayre, P.H., Stuve, O., Arnold, D.L., Wener, M.H., Georges, G.E., Wundes, A., Kraft, G.H., Bowen, J.D. High-Dose Immunosuppressive Therapy and Autologous HCT for Relapsing Remitting MS (HALT-MS). Neurology 88(9):842-852, 2017. PMID:28148635.

Georges,G.E., Storb,R. Hematopoietic cell transplantation for aplastic anemia. In: Thomas' Hematopoietic Cell Transplantation, Fifth Edition, Forman,S.J., Negrin,R.S., Antin, J.H. Appelbaum,F.R. (eds.). Chichester, U.K.: John Wiley & Sons, Ltd., Chapter 46: 517-536, 2016.