Achievements

MIMG Significant Achievements

Yvonne Chen developed a CD19/CD20 bispecific chimeric antigen receptor (CAR)-T cell therapy that was subsequently evaluated in the first investigator-initiated CAR-T cell therapy trial at UCLA. Results from the phase-1 trial show efficacy and safety profiles that outperform FDA-approved CAR-T cell therapies for B-cell lymphoma, and led to a new biotechnology company in the LA area that is now advancing the therapy in a multi-site clinical trial.

Kent Hill – our group’s discovery of Social Motility as an emergent behavior in African trypanosomes demonstrated that these single-celled parasites are capable of coordinating their activities as a group and has revolutionized the study of sensing and signal transduction in these deadly pathogens. (The work was cited by Plos Pathogens as one of the most influential discoveries in Parasitology during the first decade of Plos Pathogens).

Many and earliest (first?) atomic resolution cryoEM structures reported by the Zhou lab merit highlighting. Also, the strong influence from our department in the establishment and direction of the stem cell center and CNSI.

Hoffman - Discovery of a Temporal Signaling Code to specify Immune Responses. 

Witte’s early discovery of the tyrosine kinase activity in the ABL protein and the demonstration of the BCR-ABL oncoproteins in leukemias was one of the preclinical discoveries that led to the development of Gleevec, the first targeted therapy for chronic myelogenous leukemia.

 Witte also co-discovered the gene for Bruton's tyrosine kinase, a protein essential for normal B-lymphocyte development that, when mutated, causes the onset of X-linked agammaglobulinemia. This finding influenced the development of targeted drugs like Ibrutinib to treat leukemia and lymphoma.

Another recent milestone of the Witte Lab is the PAP project where we performed a multimodal analysis on a prostate tissue antigen, PAP, to reveal peptides restricted by MHC I. Cognate TCRs were then isolated against those candidate targets. Information regarding both the epitopes and TCRs can be beneficial in designing new treatments for prostate cancer. Our platform can also be generalizable to other cancer antigens and different HLA types.

Kohn’s clinical trials for adenosine deaminase-deficient severe combined immunodeficiency (also known as ADA-SCID or bubble baby disease), a condition where babies are born without an immune system and often don’t survive past the first two years of life, have cured more than 50 babies to date. Babies with the condition and their families have traveled to UCLA for this life-saving treatment from as far away as Lebanon and a new company was formed in 2016 to further develop the therapy and make it available at other centers and to more patients.

In addition to making fundamental discoveries about eukaryotic transcription and the functions of individual transcription factors in lymphocyte development and stimulus-induced gene expression, Smale’s lab team has used genome-wide approaches to understand the logic by which stimuli alter gene expression in mammalian cells.

In 1982 the Morrison laboratory developed the methods for expressing antibody genes in lymphoid cells. This technology made it possible to identify lymphoid specific controlling elements(enhancers) and to produce genetically engineered antibodies in the appropriate cellular environment. This approach made possible a systematic analysis of the structure/function relationships within the Ab molecule including an analysis of the role of carbohydrate in antibody function. It also made it possible to make novel antibodies and antibody based therapeutics.

Specifically, at UCLA (1984-1995), Rafi Ahmed studied memory T cell differentiation and immunity of T and B cells against viruses, such as hepatitis C and HIV in a paper that gained him notoriety in the immunology world.

Along with his exploration of the disease-causing process of the AIDS virus HIV (human immunodeficiency virus), Dr. Irvin Chen also was instrumental in identifying HTLV II, a human T-cell leukemia virus. Dr. Chen was the co-inventor of a diagnostic test for this virus currently used in blood banks throughout the world.

Professor Hong Zhou’s lab focuses on 3D structural studies of biological complexes using cryo-electron microscopy (cryoEM) and cryo-electron tomography (cryoET). These emerging methods are particularly suitable for structure determination of large molecular complexes, viruses, cellular machineries and bacterial cells. Recent efforts have focuses on developing and applying advanced cryoEM and cryoET techniques to visualize the dynamic processes of microbial infections and to decipher the mechanisms of fundamental biological processes. Dr. Zhou’s group is at the forefront in pushing the envelope of cryoEM reconstruction to atomic resolution.

Zack - Development of the first animal model for HIV pathogenesis. Development of approaches to decrease the latent HIV reservoir

NAS members

Owen Witte

Jeff F. Miller

Patricia J. Johnson

Other prestigious awards and publications in high-impact journals