Alan M. Kleinfeld

BIOPHYSICS | Adjunct Member
Phone: (858) 597-3724 | Fax: (858) 597-3804 |
Alan M. Kleinfeld

Free fatty acids (FFA) provide the major source of the body’s long term energy needs and are therefore essential for health. At the same time, disruption of the normal regulation of FFA levels by diseases such as diabetes, cancer, liver diseases and cardiovascular disease can result in serious consequences including death. The focus of our laboratory is to determine how free fatty acids are transported across cell membranes and how the levels and types of FFA change in disease. To carry out these studies we have developed molecular sensors that allow FFA to be visualized within living cells and allow the profiling of blood levels of FFA for the diagnosis of major diseases. Results from these studies raise the possibility of new therapeutic strategies for treating breast cancer.

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Ruth Gjerset

HEAD, CANCER CELL BIOLOGY PROGRAM | Member
Phone: (858) 597-3880 | Fax: (858) 597-3804 |
Ruth Gjerset

Dr. Gjerset's program addresses the biology of the cancer cell and the pathways involved in therapy resistance. The goal is to establish a rationale for improved therapeutic strategies for cancer and to identify biomarkers for diagnostic assays. Her present research program focuses on a cellular protein known as p14ARF, an important suppressor of cancer cell growth, on the regulation of the cellular enzyme, topoisomerase I, an important target for chemotherapy, and on the development of diagnostic assays for therapy resistance. Through a cross-disciplinary effort her group is also studying a novel class of inhibitors of histone acetylation, a process that is central to cellular regulation and repair of damage to DNA. These inhibitors hold promise as chemosensitizing drugs that could greatly improve the outcome of conventional therapies for a variety of cancers, and decrease therapy toxicity.

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Sophia Khaldoyanidi

STEM CELL BIOLOGY & REGENERATIVE MEDICINE | Associate Member
Phone: (858) 597-3879 | Fax: (858) 597-3804 |
Sophia Khaldoyanidi

The laboratory of Dr. Khaldoyanidi is focused on the basic biology of stem cells and on translational aspects of their use for tissue regeneration. The current projects include studies on multipotent stem cells, such as hematopoietic stem cells, mesenchymal stem cells and neural stem cells, as well as on pluripotent stem cell lines.

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Toni Ortiz

ASSOCIATE MEMBER
Phone: (858) 597-3888 | Fax: (858) 597-3804 |
Toni Ortiz

Dr. Ortiz's research interests have two main objectives: a) to understand at a molecular level the imbalance in signaling pathways that lead to a status of prolonged stress facilitating the initiation and maintenance of human disease and b) to discover novel therapies to prevent, treat and cure those pathologies.

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F. Javier Piedrafita

CANCER CELL BIOLOGY | Associate Member
Phone: (858) 597-3884 | Fax: (858) 597-3804 |
F. Javier Piedrafita

The Nuclear Hormone Receptor (NHR) superfamily of transcription factors mediate signaling by a diverse array of vitamins, hormones, and small molecules to regulate the expression of specific target genes involved in many important biological functions, such as development, metabolism, homeostasis, cell growth and differentiation, and others. NHRs regulate gene expression in coordination with an increasing number of coregulators (corepressors and coactivators). Many NHRs are involved in a variety of human diseases, including cancer. Thus ligands of RAR/RXRs (retinoids), steroid receptors (ER, AR), PPARs and others have been pursued as novel targeted therapies for the chemoprevention and treatment of cancers, including prostate, breast, lung, colon cancers as well as hematologic malignancies. Dr. Piedrafita has been working for the last decade on the mechanism of action of a family of synthetic retinoids called retinoid-related molecules (RRMs) or adamantly arotinoids (AdArs) that show strong anticancer activity. This lead to the discovery that certain AdArs induced tumor cell apoptosis independently of RAR/RXR activity, but rather by inhibiting protein kinases that are often hyperactivated in cancer, such as IKK-2. Given the RAR-mediated toxicity of classical retinoids, research is now focused in optimizing lead AdArs to eliminate RAR activity while enhancing IKK-2 inhibitory activity. Most recently, Dr. Piedrafita’s interest has been expanded to the identification and characterization of novel ligands of orphan receptors and other NHRs with strong connection in cancer.

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Clemencia Pinilla

IMMUNOLOGY | Associate Member
Phone: (858) 597-3883 | Fax: (858) 597-3804 |
Clemencia Pinilla

Dr. Pinilla has over twenty years of experience and she is recognized as a pioneer in the field of combinatorial chemistry, particularly in the use of positional scanning libraries for the identification of ligands for a wide range of targets. In particular, in immunology she has studied antibody and T cell specificity and these studies have revealed an intricate balance between polyreactivity and specificity. During the last five years, she was the Project Director of the Large Scale T Cell Epitope Discovery program at Torrey Pines lnstitute, in which she led a team of researchers in the identification of vaccinia-specific T cell epitopes from human immunized donors. She was involved in the elucidation of the specificity of T cell clones of clinical relevance in multiple sclerosis, Lyme disease and cancer using positional scanning libraries. These and other studies have involved collaborative projects with multiple investigators at Torrey Pines lnstitute and other institutions in the United States and Europe. Dr. Pinilla has authored and co-authored more than one hundred peer-reviewed publications related to the identification of ligands and characterization of molecular interactions using individual compound analogs and mixture-based libraries.

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Roy Riblet

ADJUNCT MEMBER
Phone: (858) 597-3852 | Fax: (858) 597-3804 |
Roy Riblet

The survival of complex organisms like ourselves is dependent on an immune system that wards off bacteria and viruses that infect and kill. The immune system is multifaceted, involving innate mechanisms that recognize shared general patterns on bacteria and fungi, and adaptive mechanisms that rapidly create novel and highly specific receptors for any foreign structure. In the adaptive arm B lymphocytes invent and produce antibodies, proteins circulating in the bloodstream, that bind to and inactivate bacteria and viruses.

We study basic mechanisms of the antibody response to infectious microorganisms. We are trying to understand how B cells activate their immunoglobulin (Ig) genes to produce novel, specific antibodies. We have found that the process of activating the Ig genes involves large changes in several important things, 1) their location in the nucleus and what structures they are associated with, 2) the time during the cell cycle that the genes are copied which relates to their availability for expression, and 3) their shape and structure. We are pursuing each of these findings to reveal more of how the immune system works. Increased knowledge of the basic mechanisms of immunity will provide novel avenues for therapeutic intervention, to enhance responses to infections, to modulate inappropriate responses to foreign tissue grafts or to components of self in autoimmunity as in multiple sclerosis or diabetes.

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Ingrid Schraufstatter

IMMUNOLOGY | Associate Member
Phone: (858) 597-3898 | Fax: (858) 597-5141 |
Ingrid Schraufstatter

Dr. Schraufstatter has a long-standing interest in the factors and mechanisms that cause cell migration. These factors include chemokines and the complement split products C3a and C5a, which are small-sized proteins or protein split products produced during any inflammatory process. Previously her research focused on how white blood cells are chemo-attracted by these factors in inflammation. However, it has become evident over the past decade that cancer cells and various stem cells respond to the same chemotactic stimuli: In the case of cancer cells this can result in metastasis, in the case of stem cells it allows recruitment of these cells to a site of tissue injury followed by tissue repair. Recent work in Dr. Schraufstatter’s laboratory shows that C3a and C5a are potent chemotactic factors for mesenchymal stem cells, which induce the production of various trophic factors by these cells. Current interests include determining the role of C3a and C5a in the stimulation and recruitment of adult stem cells (mesenchymal and neural stem cells), the discovery of additional chemotactic factors for these cells and definition of the signaling cascades that they activate. While these efforts are primarily directed at a better understanding of basic stem cell biology, such understanding may eventually lead to improved means of cell delivery during stem cell transplantation as well as to the identification of means to augment endogenous stem cell recruitment following tissue damage.

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