Fred S. Grodins Keynote Lecture Abstracts
Michel Sadelain, MD, Ph.D,
2024 Fred S. Grodins Keynote Lecture
Title: CD 19 CAR T cells: A Paradigm for the Living Drug Concept
Director of the Center for Cell Engineering at Memorial Sloan Kettering Cancer Center
Lecture Information:
April 11 2024 – 10:30am – 11:30am, Harlyne J. Norris Research Tower (NRT) - Aresty Auditorium, Health Sciences Campus
Abstract:
Natural immune responses fall short of eradicating tumors in most cancer patients. The genetic engineering of T cells offers a means to repurpose immune cells to remedy these limitations. The first successful embodiment of engineered immunity is chimeric antigen receptor (CAR) therapy targeting CD19. CARs are synthetic receptors that redirect and reprogram T cells to engage and eliminate cancer cells. CARs that target CD19, a cell surface molecule found in most leukemias and lymphomas, have produced remarkable responses in patients with refractory B cell malignancies. Four CD19 CAR therapies are currently approved by the US FDA. Over 1000 CAR therapy trials are currently listed on the clinicaltrials.gov website. Despite high complete remission rates obtained following a single CAR T cell infusion in patients with relapsed hematological malignancies, a number of patients will eventually relapse, pointing to the need to further improve CAR design and T cell engineering strategies to increase the antigen sensitivity and functional persistence of CAR T cells. Recent studies on the antigen sensitivity of CAR T cells have yielded valuable insights into the antigen density requirements and the role of scFv affinity and costimulatory structures incorporated into CARs to enhance tumor recognition and limit antigen escape. A novel family of CARs, termed HIT receptors, provides greater sensitivity, allowing to target tumors that escape conventional CARs. Logic-gated CAR T cells offer the prospect of more selective tumor targeting, exemplified by IF-BETTER gating. Novel CAR designs, such as 1XX, aim to reconcile the effector potency of CD28-based CARs with the greater T cell persistence afforded by 4-1BB based CARs. Genome editing is emerging as a valuable tool to transcriptionally control CAR expression, remodel the T cell receptor (TCR) and enable epigenetic programming to extend the functional persistence of immune effector cells. CAR T cells thus embody a novel paradigm for immunotherapy, providing “living drugs” for patients who fail to generate effective tumor immunity through active immunization or checkpoint blockade. The success of CD19 CAR therapy in cancer further provides a foundation for evaluating CAR T cells in other pathologies such as senescence-associated disorders and autoimmunity.
Biography:
Michel Sadelain, MD, PhD, is the Director of the Center for Cell Engineering and the incumbent of the Stephen and Barbara Friedman Chair at Memorial Sloan Kettering Cancer Center. Dr. Sadelain’s research focuses on human cell engineering and cell therapy to treat cancer and hereditary blood disorders. His laboratory has made several seminal contributions to the field of chimeric antigen receptors (CARs), from design to clinical translation. His group was the first to publish dramatic molecular remissions in patients with chemorefractory acute lymphoblastic leukemia following treatment with CD19 CAR T cells.
Dr. Cato T. Laurencin
2022 Fred S. Grodins Keynote Lecture
Title: Regenerative Engineering of Bone and Other Musculoskeletal Tissues
University Professor, Chemical and Biomolecular Engineering, Materials Science and Engineering, Orthopaedic Surgery (Medical School), Reconstructive Sciences (Dental School), at University of Connecticut
Lecture Information:
Friday, January 14, 2022 3:00 p.m. - 4:00 p.m., MCB 101
Followed by a reception from 4:00 pm to 5:00 pm - DRB Patio Open to all BME faculty, staff, students & guests
Abstract:
The treatment of injuries to bone that necessitate bone regeneration continues to be a major challenge for the orthopaedic surgeon. This burden is compounded by the constraints of supply and morbidity associated with autograft tissues, the gold standard of repair. The use of allografts, xenografts, or metal and ceramic implants overcomes many of the limitations associated with autografts but fails to provide a viable solution. We have worked in the area of engineering of bone with a focus on biomaterial selection, scaffold development, cell selection, cell material interaction, growth factor delivery, and more recently developing inducible materials.
This entire body of work over more than thirty years has made matrix-based musculoskeletal engineering a viable clinical alternative, and has motivated the establishment of a new field: regenerative engineering. Regenerative Engineering involves new technologies harnessed over the past decade: advanced materials science including nanotechnology, advanced stem cell science, morphogenesis and developmental biology cues, the knowledge and appreciation of physical forces, and clinical translation. Our work has encompassed many aspects of these new technologies and heralds a bright future for the regeneration of bone and other complex tissues.
Biography:
Cato T. Laurencin, M.D., Ph.D. is the University Professor at the University of Connecticut (one of only two at the school). He earned his B.S.E. in Chemical Engineering from Princeton, his Ph.D. in Biochemical Engineering and Biotechnology from M.I.T., and his M.D., Magna Cum Laude, from Harvard Medical School. Dr. Laurencin is a pioneer of Regenerative Engineering. He is an expert in biomaterials science, stem cell technology, nanotechnology and morphogenesis and has worked in the convergence of these areas. The American Institute of Chemical Engineers created the Cato T. Laurencin Regenerative Engineering Founder’s Award recognizing his pioneering efforts. In receiving the Spingarn Medal, he was celebrated for his exceptional career that has made him the world’s foremost engineer- physician-scientist. The American Association for the Advancement of Science awarded Dr. Laurencin the Philip Hauge Abelson Prize given ‘for signal contributions to the advancement of science in the United States’. He received the National Medal of Technology and Innovation, the nation’s highest honor for technological achievement, in ceremonies at the White House. Dr. Laurencin is an elected member of the National Academy of Engineering, the National Academy of Medicine, the National Academy of Sciences, and a fellow of the National Academy of Inventors, the American Academy of Arts and Sciences and the American Association for the Advancement of Science. Renowned internationally, he is a fellow of the National Academy of Sciences India, the Indian National Academy of Engineering, the African Academy of Sciences, The World Academy of Sciences, and is an Academician of the Chinese Academy of Engineering.
Matthew Tirrell, Ph.D.
2019 Fred S. Grodins Keynote Lecture
Title: Polyelectrolyte complexation: From phase separation to self-assembly to therapeutic nanoparticles
Professor and Dean
Pritzker School of Molecular Engineering
University of Chicago and Argonne National Laboratory
mtirrell@uchicago.edu
http://pme.uchicago.edu/
Lecture Information:
Friday, November 1, 3:00 p.m. to 4:00 p.m.
MCB (Michelson Building), Conference Room, 101
Followed by a reception right outside MCB 101 from
4:00 p.m. to 5:30 p.m. Open to all BME Faculty, Staff, and Students.
Abstract:
Polyelectrolyte complexation expands the toolset for useful self-assembled objects and materials. Liquid-liquid phase separation can be used for man-made encapsulation applications just as it has evolved for creating membrane-less intracellular compartments in biology. Micelles formed from block copolymers with electrostatically complexed cores can be made and used for therapeutic protein and nucleic acid delivery. Examples of these properties will be discussed culminating in our work on the delivery of micro-RNA inhibitors to retard undesired vascular remodeling in atherosclerosis and arterio-venousfistulae.
Biography:
In 2011, Matthew Tirrell was appointed as the founding Pritzker Director and Dean of the Faculty of the Institute for Molecular Engineering and established the first University of Chicago engineering
program, which he continues to oversee (now the Pritzker School of Molecular Engineering). Professor Tirrell simultaneously served as Deputy Laboratory Director for Science (September 2015 - April 2018) and Chief Research Officer (January 2017 - March 2018) at Argonne National Laboratory. Immediately prior to joining the University of Chicago, he was the Arnold and Barbara Silverman Professor and Chair of Bioengineering at the University of California, Berkeley, with additional appointments in chemical engineering and materials science & engineering, as well as a Faculty Scientist appointment at the
Lawrence Berkeley National Laboratory. Dr. Tirrell completed ten years as Dean of Engineering at the University of California, Santa Barbara on June 30, 2009. From 1977 to 1999, he was on the faculty of Chemical Engineering and Materials Science at the University of Minnesota, where he served as department head from 1994 to 1999. Tirrell received a B.S. in Chemical Engineering at Northwestern
University in 1973 and a Ph.D. in 1977 in Polymer Science from the University of Massachusetts. He has co-authored more than 390 papers and one book, has supervised over 95 Ph.D. students and 50 postdoctoral researchers. Professor Tirrell is a member of the National Academy of Engineering, the National Academy of Sciences, the American Academy of Arts & Sciences and the Indian National Academy of Engineering, and is a Fellow of the American Institute of Medical and Biological Engineers, the AAAS, and the American Physical Society.
Kullervo Hynynen, PhD
2018 Fred S. Grodins Keynote Lecture
Title: Non-invasive brain treatments using image-guided and modulated ultrasound beams
Department of Medical Biophysics, University of Toronto, and Sunnybrook Research Institute, Toronto, Ontario, Canada
Lecture Information:
Tuesday, November 13
3:00 pm to 4:00 pm Lecture
4:00pm - 5:30 pm Reception
Location: MCB (Michelson Building), Conference Room, 101
Abstract:
When combined with imaging-guidance focused ultrasound (FUS) provides means for localized delivery of mechanical energy deep into tissues. This focal energy deposition can modify tissue function via thermal or mechanical interactions with the tissue. MRI-guided hemi-spherical phased array technology with CT based beam modulation has made FUS treatments of brain through intact skull possible in the clinical setting. Thermal ablation of a target in a thalamus has been shown to be effective in the treatment of essential tremor and is now FDA approved. The impact of an ultrasound exposure can be potentiated by intravascular microbubbles that can enhance blood-brain barrier (BBB) permeability for a wide variety of molecules, particles and even cells. The ability to modulate the BBB has been shown to be effective in treatments of many deceases in animal models with initial patient trials showing clinical feasibility. In this talk, the progress in utilizing ultrasound phased array technology for brain treatments will be reviewed and its further potential discussed.
Biography:
Dr. Hynynen received his PhD from the University of Aberdeen, United Kingdom. After completing his postdoctoral training in biomedical ultrasound also at the University of Aberdeen, he accepted a faculty position at the University of Arizona. After, he joined the faculty at the Harvard Medical School, and Brigham and Women’s Hospital in Boston, MA. There he reached the rank of full Professor, and founded and directed the Focused Ultrasound Laboratory. In 2006 he moved to the University of Toronto. He is currently the Director of Physical Sciences Platform at the Sunnybrook Research Institute and a Professor in the Department of Medical Biophysics and Cross Appointed Professor at the Institute of Biomaterials & Biomedical Engineering (IBBME) at the University of Toronto. His research focuses on utilizing focused ultrasound for non-invasive, image-guided interventions. His work in the brain spans from developing devices and methods for focal tissue ablation in clinical testing to research for targeted drug and cell delivery and stroke treatments.
Na Ji, PhD
2017 Fred S. Grodins Keynote Lecture
Biomedical Engineering Department
Title: Probing neural circuits with shaped light
Associate Professor Departments of Physics and Molecular Cell Biology
University of California, Berkeley
Lecture Information:
Thursday, October 26, 2017
Location: EEB 132
3:00 - 4:00 pm Lecture
4:00 - 5:30 pm Reception
Abstract:
To understand computation in the brain, one needs to understand the input-output relationships for neural circuits and the anatomical and functional relationships between individual neurons therein. Optical microscopy has emerged as an ideal tool in this quest, as it is capable of recording the activity of neurons distributed over millimeter dimensions with sub-micron spatial resolution. I will describe how we use concepts in astronomy and optics to develop next-generation microscopy methods for imaging neural circuits at higher resolution, greater depth, and faster speed. By shaping the wavefront of the light, we have achieved synapse-level spatial resolution through the entire depth of primary visual cortex, optimized microendoscopes for imaging deeply buried nuclei, and developed a video-rate (30 Hz) volumetric imaging method. We apply these methods to understanding neural circuits, using the mouse primary visual cortex as our model system.
Biography:
Na Ji studied chemistry and physics as an undergraduate in the University of Science and Technology of China, then pursued her graduate degree at the University of California Berkeley. In 2006, she moved to Janelia Research Campus, Howard Hughes Medical Institute, where she worked with Eric Betzig on improving the speed and resolution of in vivo brain imaging. She started her own group in Janelia in 2011, where, in addition to imaging technology development, her lab applies the resulting techniques to outstanding problems in neurobiology.
GILDA A. BARABINO
2015 / 2016 Fred S. Grodins Keynote Lecture
Biomedical Engineering Department
Title: Cell Biomechanics and Disease
Gilda A. Barabino, Ph.D
Professor of Biomedical Engineering and Dean,
The Grove School of Engineering,
The City College of New York
CV
Lecture Information:
Wednesday, October 28, 2015
Davidson Continuing Education Center (DCC), Vineyard Room
3:00 - 4:00 pm Lecture
4:00 - 5:30 pm Reception
Abstract:
The connections between cell biomechanics and the onset and progression of human diseases is widely recognized. In the context of sickle cell disease (SCD), this presentation will illustrate the important role of biomechanics in the pathophysiology of disease and how a better understanding of biomechanics can lead to new developments in diagnosis, prognosis and treatment. SCD is a debilitating genetic blood disorder affecting 72,000 Americans and millions globally that induces chronic inflammation and vascular dysfunction and causes multiple organ damage as a result. The pathophysiology of SCD is quite complex and involves altered interactions between blood cells and endothelial cells lining the vessel walls, altered mechanical properties of blood, blood cells and blood vessels, and altered tissue properties in affected organs. Although the molecular defect associated with aberrant sickle hemoglobin is well understood and the polymerization of sickle hemoglobin and sickling of red blood cells has been extensively studied, effective treatment remains elusive. We apply mechanical approaches to elucidate mechanisms underlying disease progression to enable new therapies and provide clinicians with therapeutic opportunities for improved management of individuals with SCD. This work has implications for other diseases that cause changes in the biomechanical properties of cells.