Mara Jeffress is currently a Postdoctoral Fellow at the Lawrence Berkeley National Laboratory in Berkeley, CA. Her work on breast cancer cell signaling and drug resistance is part of a larger multi-site, multi-dicipline Integrative Cancer Biology Program (ICBP) project funded by the National Cancer Institute. Please find a brief description of that work and her previous research projects here:

Uncovering Mechanisms of Cancer Cell Resistance to MEK inhibitors (2006-present, Laboratory of Dr. Paul Yaswen, Department of Cancer Biology, Division of Life Sciences, Lawrence Berkeley National Laboratory)

Like bacteria and other infectious organisms, cancer cells can become resistant to drugs that we use to try to fight them. In my current work I am utilizing RNAi technology and large scale human genomics to discover mechanisms of cancer cell drug resistance and to look for cancer biomarkers and new drug tartgets.

Methods used: human tissue culture, including primary cell culture, drug screens, IC50 assays, viral production, shRNA and siRNA library screening, cloning, western blot, various cellular based assays.

Identification of putative mefloquine resistance genes from Plasmodium falciparum (1999-2004, Laboratory of Dr. Stanley Fields, Department of Genome Sciences, University of Washington) PubMed Abstract

Mefloquine is an effective antimalarial drug; however, resistant strains of the human malarial pathogen, Plasmodium falciparum, are beginning to arise. The yeast S. cerevisiae is sensitive to mefloquine, enabling the development of a screen for P. falciparum genes involved in drug resistance. Utilizing this screen, I identified and characterized the four genes that exhibited the strongest mefloquine resistant phenotype in yeast. All four (PFD0090c, PFI0195c, PF10_0372 and PF14_0649) are uncharacterized P. falciparum genes. In addition, I examined multiple strains of drug resistant and drug sensitive parasites to determine if any of my candidate genes have sequence or expression variations, which correspond with drug resistance. More>>

Methods used: yeast genetics, cloning, library screening, genetic screening, drug resistance assay development, primer design for quantitative RT-PCR, immunolocalization, yeast two-hybrid screening, western blot, protein purification, P. falciparum tissue culture, RNA isolation, microarray assays.

Protein-protein interactions between WW-domain containing proteins of Plasmodium falciparum (2000-2003, Laboratory of Dr. Stanley Fields, Department of Genome Sciences, University of Washington)

The WW domain is the smallest independently folding protein domain. It is found singly or repeated in a wide variety of proteins and mediates protein-protein interactions with proteins that contain regions rich in the amino acid proline. By homology searching, I identified 6 WW domain-containing proteins in P. falciparum and screened them in a yeast two-hybrid assay against the P. falciparum proteome. I found several interesting interactions with poly-proline containing proteins, including ubiquitine ligases, ribonucleases, polyA binding protein and several unknown proteins.

Methods used: yeast two-hybrid assay, library screening, cloning, western blot.

Development of high-throughput assay for screening the viruses in HIV+ patients for point mutations that confer anti-viral drug resistance (1997-1998, Dr. Scott Eastman, Division of Nucleic Acid Diagnostics, Chiron Corp., Emeryville, CA)

I was part of 6 person research and development team that created a highly sensitive, high-thruput assay to detect specific single nucleotide polymorphisms (SNPs) known to be associated with HIV drug resistance. These SNPs occur in the two genes (reverse transcriptase and protease) encoding the targets of anti-HIV drugs. Assay samples were HIV virus isolated and amplified from clinical patient samples. The assay was being developed for clinical use to predict HIV drug failure before it results in increased viral load and the related loss of patient T-cells. I was also asked by the senior scientist, Dr. Eastman, to write all of the technical documentation for this project.

Methods used: nucleic acid hybridization assays, fluorescence spectroscopy, technical writing.

Identification and characterization of a novel retinal-accepting protein from the pineal gland of the California River Lamprey (1992-1993, Laboratory of Dr. Roberto Bogomolni, Department of Chemistry and Biochemistry,UCSC)

We identified and characterized a novel retinal-accepting protein from the pineal gland. The protein was isolated by "feeding" it a radiolabeled ligand (tritiated retinal) and then reducing the Schiff's base linkage between the protein and ligand followed by autoradiography. This novel protein had the characteristic spectroscopic pattern of other retinal proteins but a size intermediate to rhodopsin proteins of the mammalian visual system and the bacterial opsins, suggesting that an evolutionary intermediate between the two still exists within the light-sensing pineal gland (the "third eye") of fish.

Methods used: protein purification, various spectroscopic methods, radiolabeling, autoradiography, brain dissection.