2020 Faculty Talks

Alexander Hoffmann, UCLA

Understanding Lymphoma in terms of intra-cellular molecular networks

Abstract description TBA

Crystal Rogers, UC Davis

Identifying links between cell adhesion in embryonic development to disease

Abstract description TBA

Kevin Corbett, UCSD

Unintended consequences: How studying meiosis helped us understand DNA repair in Cancer

Abstract description TBA

John Termini, City of Hope

Title and abstract TBA

Dr. Carolynn Arpin, CSU Chico - Biology

A Novel Antagonist of Growth Factor Receptor-Bound Protein-2 (GRB2) Inhibits Leukemic Proliferation

The majority of chronic myeloid leukemia (CML) cases are caused by a chromosomal translocation linking the breakpoint cluster region (BCR) gene to the Abelson murine leukemia viral oncogene-1 (ABL1), creating the mutant fusion protein BCR-ABL1. Downstream of BCR-ABL1 is growth factor receptor-bound protein-2 (GRB2), an intracellular adapter protein that binds to BCR-ABL1 via its src-homology-2 (SH2) domain. This binding constitutively activates growth pathways, downregulates apoptosis, and leads to an overproliferation of immature and dysfunctional myeloid cells. Utilizing novel synthetic methods, we developed four furo-quinoxaline compounds as GRB2 SH2 domain antagonists with the goal of disrupting this leukemogenic signaling. One of the four antagonists, NHD2-15, showed a significant reduction in proliferation of K562 cells, a human BCR-ABL1+ leukemic cell line. To elucidate the mode of action of these compounds, various biophysical, in vitro, and in vivo assays were performed. Surface plasmon resonance (SPR) assays indicated that NHD2-15 antagonized GRB2, binding with a KD value of 119 ± 2 μM. Cellulose nitrate (CN) assays indicated that the compound selectively bound the SH2 domain of GRB2. Western blot assays suggested the antagonist downregulated proteins involved in leukemic transformation. Finally, NHD2-15 was nontoxic to primary cells and adult zebrafish, indicating that it may be an effective clinical treatment for CML.

Dr. Marcell Dougan, San Jose State - Public Health

A Mobile Application for Improving the Quality of Life among Multi-Ethnic Breast Cancer Survivors

In recent years, there has been a proliferation of mobile applications for health; however, few of these applications are comprehensive. To understand key factors that drive use of mobile applications among breast cancer survivors, semi-structured interviews were conducted with survivors and individuals in their support systems. We interviewed a convenience sample of 11 ethnically diverse participants. Six were breast cancer survivors, one was a survivor of a different type of cancer, and four were either caregivers, clinical professionals, or research professionals. Interview transcripts were analyzed using thematic analysis. Factors emerged in two overarching thematic areas: 1) finding meaningful support and 2) ensuring utility of a mobile application. In relation to meaningful support, participants identified three important factors: increasing social support and connection, motivation for self-care, and assistance navigating healthcare. In the area of application of utility, participants identified three key considerations: keeping a user-friendly interface, ensuring credible information, and using the data collected for the purposes intended. It is important to consider factors associated with both meaning and utility when developing a mobile application for breast cancer survivors. More research is needed with breast cancer survivors of more ethnic minority groups, as they may identify other important areas for consideration.

Dr. Cory Brooks, CSU Fresno - Chemistry/Biochemistry

Impact of Tumor Specific O-Glycosylation on Therapeutic Antibody Recognition of Mucins

The stunning clinical success of new antibody-based therapies for cancer treatment has transformed immunotherapy into a “fifth pillar” of oncology. Key to the successful application of immunotherapy is a cancer specific target. Overexpression of mucin family glycoproteins has been linked to poor prognosis and metastasis in pancreatic and breast cancer patients. A common feature of cancer associated Mucin expression is altered O-glycosylation, a morphological change which can be exploited for the generation of new immunotherapies. We investigated how the binding of the therapeutic antibody AR20.5 was influenced by Mucin glycosylation. We explored the affinity of AR20.5 to a cancer specific MUC1 glycopeptide and peptide. The antibody bound the glycopeptide with an order of magnitude stronger affinity than the peptide. Using a combination of X-ray crystallography, NMR and molecular dynamic simulations we determined that the high affinity binding of AR20.5 to glycosylated MUC1 is not driven by specific antibody-antigen contacts, but rather is governed by carbohydrate induced alterations to the conformational equilibrium of MUC1. This study demonstrated a novel mechanism of antibody-antigen interaction and also suggests that glycosylation of MUC1 is an important consideration for the generation of high affinity therapeutic antibodies.