Overview
Our research uses state-of-the-art bioengineering methods to develop improved cell-based therapeutics to treat cancer and inflammatory diseases. Our research and educational programs cover a broad scope of multidisciplinary areas including cancer biology, immunology, virology, cell engineering, genetic engineering, signal transduction, biotechnology, and preclinical as well as clinical medicine. UCSD is an outstanding research university within an excellent and interactive community situated in the heart of San Diego’s academic research and biotechnology Mecca. The Moores Cancer Center, UCSD Medical Center, and the La Jolla scientific community provide an outstanding intellectual environment and an excellent place to work and live http://www.sandiego.gov. Also, Cytonus Therapeutics (https://cytonus.com) is developing bioengineered cell therapeutics for the treatment of cancer and inflammatory diseases in close association with our lab. Several integrated academic and corporate training and job opportunities in biotechnology are available through Cytonus and UCSD. We offer an excellent salary and benefits package commensurate with the candidate’s skills and experience. Candidates with abilities to work independently and collaboratively, identify and execute research priorities, multitask different projects and take initiative are encouraged to apply. Strong interpersonal and leadership skills, and outstanding verbal and written communication skills are required. Current job openings in the Klemke lab are described below. Candidates with research interests and skills outside the specific scope of these projects are also encouraged to apply after contacting Dr. Klemke. Please send curriculum vitae, contact information and a brief statement of research and career goals to Dr. Richard Klemke (rklemke@ucsd.edu).
Post Doctoral Research Associate Positions Available in the Following Research Areas:
1. Genetic and Molecular Engineering of Novel Cargocyte-based Biotherapeutics to Treat Cancer and inflammatory diseases.
Description: Effective January 5, 2019. Cell-based therapeutics is a rapidly evolving science that uses genetic modification of cell-based products to treat a wide range of diseases. The long-term outlook for research careers in cell-based therapeutics and biomedical engineering is outstanding. Two postdoctoral positions are available to study the underlying mechanisms that facilitate Cargocyte cell migration and homing to the primary tumor and metastatic sites. Researchers will use a combination of state-of-the-art genetic and cell engineering methods, cell-based in vitro assays of cell homing, and novel preclinical animal models to unravel the molecular mechanisms that guide Cargocytes to the tumor/mets. Building on this mechanistic knowledge, researchers will: (1) genetically engineer Cagocytes to express various forms of enhanced cell guidance and vascular adhesion receptors (e.g. CXCR4, CCR2, and PSGL-1, etc); (2) use cell engineering methods (e.g. FACS sorting, single cell cloning etc) to isolate high expressing cell factories; (3) genetically engineer Cargocytes to produce various novel therapeutic agents alone or in combination (e.g. immune modulating cytokines IL-12, IL-15, GM-CSF, therapeutic antibodies CTLA-4, PD1/PDL1, and miRNAs, etc); (4) test these novel cell therapeutics for homing and cargo deliver in mouse models of pancreatic cancer, breast cancer, and in a standard ear inflammation model.
Required Education and Qualifications:
MD or Ph.D. or equivalent strong work experience in molecular biology and gene engineering technologies such as CRISPR, integrating lentiviruses, and transposons is required. Previous experience in FACS analysis, FACS sorting, cell cloning, cell migration, immune cell culture, ELISA, fluorescence microscopy is beneficial.
2. Positions in the Immunotherapy and Immune Oncology Group
Description: Effective January 5, 2019. Senior Project Scientist leader position (2-5 years previous experience) and several postdoctoral positions (0-2 years previous experience) are available in immune oncology and immunology. Candidate will study how adoptive cell-based therapeutics can be utilized to modulate the innate and adaptive immune systems to fight advanced stage metastatic cancers and treat inflammatory diseases. Candidate will collaborate closely with other immunologists and molecular biologists at UCSD and the Moores Cancer Center to gain a deep understanding of the mechanisms driving tumor immune recognition, immunosuppression, and tumor cell immune evasion. Building on this mechanistic knowledge, researchers will design and test their novel approaches/concepts to treat cancer and inflammatory diseases using cell-based therapeutics such as Cargocytes and other immune-activating cells (CAR-T, NK, TILs, etc). Immunologists will also work closely with the bioengineering group to design and develop novel cell therapeutics capable of delivering to the tumor and inflammatory sites various immunomodulatory payloads (e.g. cytokines, checkpoint antibodies, etc).
Required Education and Qualifications
MD or Ph.D. or equivalent strong work experience in immunology. Hands on experience in designing and executing a wide range of immunological assays including antigen-specific CTL activation/killing, immune cell proliferation, ELISPOT assay, splenocyte assays, immune cell profiling by FACS and qPCR, and IHC to detect various immune cell subpopulations in tissues. Knowledge of molecular biology methods and experience with preclinical mouse models that reflect human immune responses would be highly beneficial.
3. Positions in Oncolytic Virology
Description: Effective January 5, 2019. Oncolytic virus therapy is one of the most exciting and promising areas in cancer research. However, there is a significant need to develop biocompatible carriers that improve systemic delivery of oncolytic viruses and target them to primary and metastatic tumors. Cargocytes engineered to express tumor-homing receptors have the potential to substantially improve systemic administration and delivery of oncolytic viruses by shielding them from immune recognition until reaching the target tissue. The overall goal of this project is to understand the underlying mechanisms that drive anti-tumor immune responses induced by Cargocyte-mediated viral therapy. Postdoctoral positions are available to study the underlying mechanisms of virus/host interactions and how these interactions can be harnessed to successfully treat metastatic cancers. The candidate will investigate how Cargocytes armed with oncolytic viruses (oVSV, oHSV, oMSV) home to tumors, induce localized inflammation, induce innate/adaptive immune responses, and determine how infiltrating immune cells respond to known and novel tumor-specific antigens. The researcher will also investigate in detail how Cargocyte-mediated virotherapy augments anti-tumor immunity in combination with GM1215 and immune checkpoint inhibitors to improve treatment of metastatic disease.
Required Education and Qualifications
MD or Ph.D. or equivalent strong work experience in immunology and virology. This postdoctoral position requires experience in molecular virology with specific focus on virus gene engineering technologies and a deep understanding of virus replication concepts as it relates to cancer and gene therapy applications. The ideal candidate also has previous experience in culture of diverse mammalian cell lines, cell-based assays for virus characterization and quantification (e.g. plaque assays, virus replication, virus neutralization, cell viability, cell lytic assays, PCR of viral products). Knowledge of antiviral or anti-tumoral immune responses and hands on experience with preclinical mouse models of cancer are a strong plus.
4. Signal Transduction and Cell Biology: Signaling mechanisms of cell migration and cancer metastasis
Description: Effective January 5, 2019. Postdoctoral positions are available to study the molecular signaling mechanisms that mediate cell migration and cancer cell metastasis. Postdoctoral fellows will use biochemical methods to study how cell surface receptors interpret extracellular cues and integrate these signals into intracellular signaling modules and scaffolds that regulate the migration machinery of the cell. Mechanistic studies will determine how G protein-coupled, tyrosine kinase, and adhesion receptors transmit signals that control the actin-myosin cytoskeleton to mediate cell movement, and determine how motile cells strategically position these signaling modules in the cell body and pseudopodium to target unique effector proteins. Researchers will utilize state-of-the-art molecular biology, biochemistry, proteomic, and fluorescence protein technologies as well as confocal and two-photon microscopy. The candidate will obtain an in depth knowledge of contemporary mechanisms of signal transduction and propagation as it relates to cell movement in healthy and diseased cells. The candidate will also work closely with clinicians and informatics experts at the Moores Cancer Center to obtain knowledge about deregulation of cancer cell signals as it relates to clinical and animal models of cancer progression.
Required Education and Qualifications
MD or Ph.D or equivalent work experience. The candidate must be experienced in molecular biology and cell culture and be familiar with protein biochemistry. Experience with epifluorescence and confocal microscopy would be highly beneficial. ·Ability to work independently and collaboratively, identify and execute research priorities, multitask different projects and take initiative. ·Strong interpersonal and leadership skills, and outstanding verbal and written communication skills.
5. Signal Transduction and Cell Biology: Investigating novel phosphoproteins and kinase signaling networks that control cell migration and cancer metastasis.
Description: Effective January 5, 2019. Postdoctoral positions are available to investigate novel phosphoproteins and kinase signaling networks that control immune cell homing, cancer cell migration, and metastasis. We have used large-scale proteomic, phosphoproteomic, and bioinformatics methodologies to identify novel proteins and map signaling networks that control chemokine sensing, cell polarization, invadopodia formation, migration, and cancer cell metastasis. PNAS 104:8328. 2007. Curr. Opin. Cell Biol. 24:662-669. 2012). Several important new cytoskeletal-associated kinases, novel phosphorylation sites, and key signaling proteins have been identified and are now ready for physiological testing using RNAi knockdown technology, cell-based assays of immune cell trafficking, cell migration/metastasis, molecular biology, and confocal microscopy. The researcher will perform structure-function studies to determine how these new phosphoproteins and kinases couple to the migration and metastatic machineries of the cell and determine whether they are deregulated in cancer patients using various cell-based models, tissues specimens, immunohistochemistry, and molecular gene profiling methods.
Required Education and Qualifications
MD or Ph.D or equivalent work experience. · The candidate must be experienced in molecular biology, cell culture, and protein biochemistry. Experience in immunology and confocal microscopy would be highly beneficial. ·Ability to work independently and collaboratively, identify and execute research priorities, multitask different projects and take initiative. ·Strong interpersonal and leadership skills, and outstanding verbal and written communication skills.
6. Cancer Biology and Genetically Engineered Mouse Models of Cancer: Investigating the role of PEAK1 tyrosine kinase in cancer progression, cell metastasis and immune functions using a newly developed conditional PEAK1 knockout mouse.
Description: Effective January 5, 2019. Two postdoctoral projects are available to study the function of PEAK1, a newly discovered kinase that is a critical player in several human cancers including PDAC, colon, and breast cancer.
Project 1. To directly address the function of PEAK1 in PDAC, conditional PEAK1 knockout mice have been engineered in our lab using Cre-lox technology. Researchers will breed PEAK1 knockout mice to genetically engineered mouse (GEM) models of PDAC (e.g. LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre) to determine how PEAK1 contributes to cancer formation, cancer stem cell propagation/differentiation, tumor progression, metastasis, and drug resistance mechanisms.
Project 2. Recent work indicates that PEAK1 plays a role in normal immune functions of the body. The objective of this project is to determine how PEAK1 signaling controls B-cell propagation and differentiation, and natural kill cell functions including cell homing to tumors and directed cell killing mechanisms.
Required Education and Qualifications
MD or Ph.D or equivalent work experience. Knowledge of cancer, immunology, molecular and cell biology, and mouse husbandry required. Ability to work independently and collaboratively, identify and execute research priorities, multitask different projects and take initiative. ·Strong interpersonal and leadership skills, and outstanding verbal and written communication skills.
Other projects in the general areas of cancer cell biology, immunology, and vascular biology may be developed upon discussion with the research supervisor in regard to the student's specific training/research goals.
Salary and benefits commensurate with experience. Please send curriculum vitae and a brief statement of research and career goals to rklemke@ucsd.edu.