Betty Booker, Ph.D. Email and Phone Number

The Probe Design Team uses bioinformatic pipelines with a deep understanding of spatial biology and genomics to build, develop, & expand tools for the RNAscope family of products.

The systematic identification of the molecular basis causing Mendelian genetic disease (a single mutation in a single gene leads to a specific disease) has been extremely successful with an estimated characterization of ~1,200 different disease-causing genes cloned. Conversely, the identification of nucleotide changes leading to human disease in noncoding sequences (not genes), which span 98% of our genome, has not been that successful. There is a variety of clinical and molecular data supporting the idea that noncoding sequences that function as regulatory elements (regions that turn on and off genes at different timepoints, locations, amounts) can harbor mutational events that lead to human disease. However, the identification of distinctive nucleotide changes within these elements that lead to human disease has been extremely limited due in part to the vast genomic non-coding space in which to search for them, their scattered distribution, the unavailability of an established regulatory code (unlike genes where we know their code for amino acid sequence), and the difficulties in linking these elements to specific genes. Through a combination of comparative genomic strategies, regulatory element analysis, human patient samples, and mouse and fish genetic engineering technologies, we are working to elucidate mechanisms whereby genetic variation within these sequences lead to changes in human phenotypes.

UCSF IRACDA combines a traditional mentored postdoctoral research experience with an opportunity to hone additional academic skills and career development activities such as scientific writing, grant writing, and career seeking advice from former scholars. A second component of our program partners our scholars with faculty at San Francisco State University to learn pedagogy and actively teach undergraduate, masters, and graduate level classes at their institution. Finally, The Program encourages our scholars to mentor SFSU undergraduates, masters and graduate students in lab and provide outreach to the underrepresented scientific community through programs such as SFSU’s BUILD, RISE, MARC, BRIDGES, and SRTP programs.

Understanding how and why the chromosome is organized and so efficiently replicated is of major interest in the bacterial genetics community. The bacterial chromosome was initially described as a static entity with a minimal role in cellular functions. It has since been observed as having dynamic and static features. The bacterial chromosome was also believed to have evolved independently from the eukaryotic system due to its lack of homology to the organization of the eukaryotic system. The principle goal of our lab is to understand the role of chromosomal dynamics during various chromosomal processes such as transcription-induced barriers, Mu Transposition, Domain barrier formation, and superhelical densities of Salmonella typhimurium LT2 and Escherichia coli K12. A major aim for my thesis is investigating a molecular model for how negative supercoiling generated by high levels of transcription alters chromosome structure and function. Gamma Delta-Resolution assays measure the ability of the chromosome intervals to resolve two res sites in a plectonemic synapse. Previous work from our lab led to the discovery that movement of RNA polymerase in zones of high transcription remodeled DNA domains into specific loops. The analysis showed negative supercoils were generated upstream of transcription, but that contrary to conventional wisdom, positive supercoils were not found downstream of the transcription terminator. Using Lambda-Red Recombineering, I have developed Salmonella typhimurium strains that allow me to carry out similar studies on two different ribosomal RNA operons, which are among the most highly transcribed genes in bacteria, but not translated. Another aim is to understand the inverse relationship: the effects of supercoils on the level of transcription. Using the Beta-galactosidase enzyme to assay the levels of transcription upstream and downstream from highly active regions will enable us to observe any influences topology may have on transcription.

As a student intern in the department of Pulmonary and Critical Care Medicine, my research focused on pulmonary edema and other pulmonary diseases. The investigation of barrier restoration property after barrier breach is important in understanding how the endothelial barrier recovers. Sphingosine 1 Phosphate (S1P), a lipid released by platelets, has been shown to increase transendothelial electrical resistance (TEER), and therefore decrease vascular permeability. This response is observed in human pulmonary macro- and microvessel endothelial cells. However, rat macrovessel endothelial cells decreases in TEER while rat microvessel endothelial cells respond similar to human cells. Protein Kinase C (PKC) has been implicated as a key protein in the signal transduction pathway. Through classical proteomic techniques, my findings suggest that PKC-delta may exist in the active form, therefore contributing to the differential response to S1P.

The project in this laboratory was to identify certain signal transduction molecules that give rise to tumor cells when specific inhibitors are used to block the pathways of those molecules. When the pathways are inhibited, the Primordial germ cells will either proliferate in number or decrease in number. Enhanced proliferation of germ cells is called tumorigenesis, loss of germ cells is called sterility. My research determined that the RAS/MEK pathway is completely necessary for the survival of PGC’s. Blocking this pathway with PD980589 and HR12 92% of the PGC’s died, meaning this specific pathway is essential to the proliferation of PGC’s.