Meet Our Scientists

Our mission is not only to conduct scientific research, but also to ensure that our research discoveries make a difference to humans. We accomplish this by supporting our scientists in their endeavors to publish, to travel worldwide in order to give lectures and other presentations, to establish and maintain collaborations with other scientists, and to act as mentors to students and young scientists just beginning in their careers. Throughout the year, Torrey Pines Institute scientists traveled throughout the United States and worldwide to share research results, to learn of others’ research, and maintain important collaborative efforts.

All Principal Investigators adhere to the TPIMS financial conflict of interest policy which can be found here.

Colette Dooley

Pain Management | Assistant Member
Phone: (772) 345-4709 | Fax: (772) 345-3649 |
Colette Dooley

Dr. Dooley uses her training in combinatorial libraries and fluorescent imaging to research new methods for pain relief, addiction and food regulation, and investigates cells' response to stresses which may lead to a better understanding of pain management, chronic pain, addiction, Parkinson's and Alzheimer's.

Read more

Marc Giulianotti

CHEMISTRY | Director of Chemistry Operations
Phone: (772) 345-4729 | Fax: (772) 345-3649 |
Marc Giulianotti

Mr. Giulianotti’s research focuses on identifying potential human therapeutics and diagnostics as well as agricultural treatments. The research group combines novel approaches in combinatorial chemistry, computer-aided drug design and mathematics. The research group is currently involved in a number of different interdisciplinary projects with internal and external collaborators focusing in areas such as pain management, cancer, obesity, stroke and citrus greening.

Read more

Madepalli Lakshmana

NEUROBIOLOGY | Associate Member
Phone: (772) 345-4698 | Fax: (772) 345-3649 |
Madepalli Lakshmana

The primary research interest of my group is to understand molecular mechanism for the reduced synaptic connections in Alzheimer’s disease (AD) leading to loss of memory, a seminal feature of AD. AD is characterized by the presence of intracellular neurofibrillary tangles and extracellular amyloid plaques believed to be responsible for loss of synapses. The long-term objective of my research is to discover molecular targets which may modulate generation of amyloid beta peptide (Ab), the core constituent of amyloid plaques. Additionally, we are interested to investigate whether critical regulators of spine generation and maintenance can be used as therapeutic targets in AD since loss of synapses is a crucial factor for the cognitive deficits in AD.

In spite of rigorous research efforts worldwide, currently there is not a single drug available that can effectively reverse or even slow down the loss of memory in patients with AD. Therefore our goal is to use proof-of-concept molecules which modulate Ab generation and/or number of spines to discover lead compounds using varieties of small molecule and peptide libraries by high throughput screening (HTS). To accomplish these objectives we will use histological, pharmacological, biochemical and molecular approaches by using varieties of techniques including immunoprecipitation, yeast two-hybrid screening, in vivo lentiviral delivery, transgenic mouse models, knockout mouse models, high throughput robotics screening and TR-FRET imaging.

Read more

Yangmei Li

CHEMISTRY | Senior Scientist
Phone: (772) 345-4725 | Fax: (772) 345-3649 |
Yangmei Li

My research interest focuses on the development of new methodologies for the synthesis of bioactive compounds, particularly cyclic peptides and heterocyclic compounds. I am also interested in developing novel ‘volatilizable’ supports for organic synthesis. My current research interest is total synthesis of natural cyclic peptides (cyclic depsipeptides) and their analogs for targeting different diseases including bacteria resistance, cancer, inflammation, and pain.

Read more

Karina Martínez Mayorga

Phone: (772) 345-4688 | Fax: (772) 345-3649 |
Karina Martinez Mayorga

Dr. Martínez-Mayorga focuses on the development of structural models by computational and spectroscopic techniques to aid in the design of new compounds that may be used to treat disease. Some of the computational methods employed in our research group are: conformational analysis, molecular similarity searching, ligand-based virtual screening, quantum chemical calculations, and molecular dynamics simulations. The spectroscopic characterization is primarily based on nuclear magnetic resonance experiments. In close collaboration with national and international research groups, we are developing structural models with relevance to treating a variety of health-related conditions such as diabetes, pain, cancer, as well as the vision process. In addition, we are studying the importance of flavor chemicals on mood and exploring the use of metal complexes to combat serious but neglected tropical diseases.

Read more

Jose Luis Medina-Franco

Phone: (772) 345-4685 | Fax: (772) 345-3649 |
Jose Medina

Dr. Medina-Franco's research focuses on computer-aided drug design. The research group conducts virtual screening of large compound databases to identify novel compounds directed to targets associated with the treatment of cancer, HIV/AIDS and other diseases. Molecular modeling and chemoinformatic methods are used for the structure-based and ligand-based optimization of bioactive compounds. The group also performs structural classification, diversity analysis and data mining of chemical libraries. Current projects include:

Read more

Adel Nefzi

ASSOCIATE MEMBER | Director of Chemistry
Phone: (772) 345-4739 | Fax: (772) 345-3649 |
Adel Nefzi

The central focus of my work is the development of efficient approaches to the synthesis of novel small molecule and macrocyclic compounds. All of the libraries prepared are being made available to the scientific community through the Institute Biological Outreach Program for the identification of new hits as first steps of an optimal “design and selection” process for lead optimization for the development of new pain management, cancer, tuberculosis and antimicrobial drugs.

Read more

Greg Welmaker

Chief Operating Officer / Director of Drug Discovery
Phone: (772) 345-4582 | Fax: (772) 345-3649 |
Greg Welmaker

Dr. Welmaker is an experienced medicinal chemist having worked in the biotechnology and pharmaceutical industry for over 15 years. During this time, he led teams in both the early and late stages of drug discovery. At Torrey Pines Institute, he continues to utilize these experiences to help identify new compounds suitable for advancement into human clinical trials.

Read more

Richard A. Houghten

Phone: (858) 597-3805 | Fax: (858) 597-3804 |
Richard Houghten

Richard A. Houghten, is the founder and President of Torrey Pines Institute for Molecular Studies. The Institute was founded in 1988, and began its operations in 1989 with eight employees. Now in its 22nd year, it has become internationally recognized for its scientific contributions in a wide range of fields, including chemistry, multiple sclerosis, diabetes, immunology, infectious disease, heart disease, cancer vaccines and pain management. The institute has grown to include over 150 scientists, technicians and administrative staff, all of whom work in an environment that emphasizes personal and professional growth by encouraging the development of independent research ideas as well as the development of collaborative efforts with scientists throughout the world.

Read more

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.

Read more

Ruth Gjerset

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.

Read more

Sophia Khaldoyanidi

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.

Hyaluronan, a long-chain polysaccharide with a key role in bone marrow

Dr. Sophia Khaldoyanidi, Associate Member at Torrey Pines Institute for Molecular Studies (TPIMS), and her team of international collaborators recently discovered that the long-chain sugar molecule hyaluronan is important for the production of new blood cells in bone marrow. Millions of patients around the world suffer from acute and chronic illnesses caused by blood cell deficiencies resulting from damage to the bone marrow by chemotherapy, radiation, or disease. The new study, published in the July 20th, 2012 issue of the Journal of Biological Chemistry, could pave the way for new therapies that facilitate production of blood cells and improve the way that bone marrow stem cells are used to treat disease.

What is hyaluronan?

Dr. Khaldoyanidi’s team were interested in whether a long-chain polysaccharide called hyaluronan plays a role in supporting the production of new blood cells in the bone marrow, a process termed hematopoiesis. Hyaluronan is composed of repeating disaccharide units (N-acetyl-D-glucosamine and glucuronic acid) and is synthesized throughout the body by three hyaluronan synthase enzymes. Hyaluronan was initially thought to function simply by maintaining extracellular space. However, later studies showed that it participates in local extracellular matrix assembly by interacting with a variety of molecules, and is involved in the regulation of multiple cell functions, including cell proliferation and migration. As expected, hyaluronan concentrations are normally exquisitely regulated by synthetic and catabolic enzymes, but in some diseases, patients have abnormal serum levels of hyaluronan. Abnormalities in bone marrow hyaluronan levels can be induced by many external factors including radiation and chemotherapeutic treatments.

Stem cells and their microenvironment

Hematopoietic stem cells (HSCs) colonize the bone marrow during fetal development and remain there throughout life, generating a variety of lineage-specific progenitor cells that give rise to billions of blood cells every day. This process, termed hematopoiesis, is regulated by the local bone marrow microenvironment. The microenvironment is composed of several distinct cell types, including cells of mesenchymal origin, which communicate with each other and with HSCs through secreted regulatory molecules and cell surface interactions. The microenvironment influences many HSC decisions, including whether to undergo proliferation versus quiescence, self-renewal versus differentiation, or survival versus apoptosis. The health of this microenvironment is particularly important for patients undergoing bone marrow or stem cell transplantation, because the microenvironment regulates functions of donor HSCs in the recipient patient’s bone marrow.

“Although the quantity and quality of transplanted HSC are important for the recovery of hematopoiesis in patients, the functional status of the regulatory hematopoietic microenvironment is a critical parameter that determines the regenerative function of HSC,” said Dr. Khaldoyanidi. The success of HSC transplantation depends on the ability of the regulatory microenvironment to support hematopoiesis, which may be compromised during disease or following certain drug treatments. Thus, the hematopoietic microenvironment should be treated and allowed to recover prior to HSC transplantation. To do this effectively, it is important to understand which of the molecular pathways regulating the microenvironment’s functions are disrupted under specific pathological conditions.

Bone marrow cultures show hematopoietic cells (visible as small bright round cells) and components of the microenvironment (visible as a lower layer of dark and adherent cells). Cultures treated with the chemical 4-methylumbelliferone (4MU), an inhibitor of hyaluronan synthesis, (right) show a dramatic reduction in numbers of hematopoietic cells compared with untreated cultures (left).

How hyaluronan regulates HSCs

In the new study, Dr. Khaldoyanidi and her collaborators used a mouse engineered to delete the three hyaluronan synthase genes Has1, Has2, and Has3 (these mice are termed Prx1-Cre;Has2flox/flox;Has1–/–;Has3–/– triple knockout mice), which lacked hyaluronan in the bone marrow microenvironment. In these animals, hematopoietic progenitors — the cells that produce mature, functionally active blood cells — relocated from their normal niche in the bone marrow to sites such as the spleen and liver. In addition, hyaluronan-deficient bone marrow cells could not support growth of HSC in cell culture, which was consistent with the in vivo findings that hyaluronan is essential for HSC function.

“Many past studies have hinted at a role for hyaluronan in hematopoiesis. Focus on the biology of hyaluronan in this fundamental process was rewarded when the recent report by Goncharova and co-workers confirmed that hyaluronan is essential for bone marrow hematopoiesis. The study is one of the more comprehensive efforts in years to determine if this polysaccharide plays a key role in allowing people to make many types of new blood cells every day,” said Dr. Paul H. Weigel, Professor and Chairman at the University of Oklahoma Health Sciences Center and President of the International Society of Hyaluronan Sciences ( “These research findings are important because they bring us closer to a future ability to manipulate the complicated cellular pathways that utilize and respond to hyaluronan, in order to improve the efficacy of using stem cells to treat a variety of diseases.”

“It is an interesting and important study that demonstrates that hyaluronan has important and essential roles in bone marrow stem cell niches that foster hematopoietic progenitor cells. Here at the Cleveland Clinic we have shown that progenitors for osteogenic lineage in human bone marrow isolates can be significantly enriched by selecting for cells with hyaluronan coats. This paper has now been accepted in Annals of Biomedical Engineering, and would complement and compliment Sophia’s study,” said Dr. Vincent Hascall, Professor at the Cleveland Clinic Lerner Research Institute.

Once Dr. Khaldoyanidi’s team had shown that hyaluronan was needed for normal bone marrow function, the researchers used the chemical 4-methylumbelliferone (4MU) to inhibit the production of hyaluronan by cultured bone marrow cells. They showed that 4MU decreased the expression of hyaluronan synthases (HAS2 and HAS3), inhibited hyaluronan synthesis, and eliminated hematopoiesis in the culture dish. Further studies demonstrated that endogenously produced hyaluronan was needed for the production of chemokines and growth factors, which in turn were necessary for the motility of hematopoietic cells. Hyaluronan was also found to be involved in regulating interactions of the hematopoietic cells with the vasculature under conditions of physiological blood flow.

This and other studies have shown that too much or too little hyaluronan in bone marrow caused hematopoietic abnormalities. Thus, in healthy tissues, the body maintains optimal hyaluronan levels through complex machinery that fine-tunes hyaluronan synthesis, binding, retention, accumulation, degradation, and clearance. Collectively, this new study suggests that the tissue-associated hyaluronan in bone marrow might be clinically relevant and reflect the biological health of the hematopoietic microenvironment.

Faculty of 1000

The study was evaluated by the Faculty of F1000, in which the world's leading scientists and clinicians identify and evaluate the most important articles in biology and medical research. On average, 1500 new evaluations are selected each month, which is about 2% of all published articles in the biological and medical sciences.

“This is a highly prestigious distinction that highlights the quality of Dr. Khaldoyanidi's scientific work,” said Dr. Robert Sackstein, a leading bone marrow transplant physician-scientist and Professor,Harvard Medical School. “Dr. Khaldoyanidi's elegant studies provide seminal evidence of the key role of hyaluronan in the hematopoietic microenvironment. The work has profound implications for clinical practice, as it suggests that maintenance of marrow hyaluronan levels could improve blood cell development.” Dr. Hascall concurred. “The fact that the Faculty of 1000 is now paying attention to hyaluronan research is great. As most of us in the field know, it has been difficult at times to get the broader research community to pay attention to hyaluronan matrices and their roles in normal and pathological processes,” he said.

For patients undergoing treatment in preparation for stem cell transplantation, the team suggests it may prove clinically useful to monitor hyaluronan recovery to help pinpoint the optimal time for stem cell transplantation. The scientists believe that biologically active hyaluronan polymers or hyaluronan synthesis inhibitors may prove useful in the clinic to correct misbalanced hyaluronan levels.

“Our findings suggest that hyaluronan is a biologically active component of the hematopoietic microenvironment and is involved in regulating hematopoietic homeostasis,” said Dr. Khaldoyanidi. “This is a very difficult time for biomedical research funding, but I am optimistic that our team will be able to continue this important project, which is on the edge of glycobiology and stem cell biology, to bring our understanding of hyaluronan biology to the next level.” The researchers in Dr. Khaldoyanidi’s group believe that further research is required to bring the recent advances in hyaluronan basic research generated in many laboratories over the past decade to the level that could finally benefit patients, i.e. to the bedside.


Researchers involved in this study were: Valentina Goncharova, Ingrid Schraufstatter, Tatiana Povaliy, Valentina Wacker, Audrey de Ridder, and Sophia Khaldoyanidi from Torrey Pines Institute for Molecular Studies, San Diego, CA; Naira Serobyan from La Jolla Institute for Molecular Medicine, San Diego, CA; Shinji Iizuka and Yu Yamaguchi from Sanford-Burnham Medical Research Institute, La Jolla CA; Irina A. Orlovskaja from Institute of Clinical Immunology, Novosibirsk, Russia; Naoki Itano from Kyoto Sangyo University, Kyoto, Japan; and Koji Kimata from Aichi Medical University, Nagakute, Japan.

Original paper: Hyaluronan expressed by the hematopoietic microenvironment is required for bone marrow hematopoiesis. Goncharova V, Serobyan N, Iizuka S, Schraufstatter I, de Ridder A, Povaliy T, Wacker V, Itano N, Kimata K, Orlovskaja IA, Yamaguchi Y, Khaldoyanidi S. J Biol Chem. 287, 25419–25433, 2012. PMID: 22654110

Dr. Khaldoyanidi’s laboratory 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 somatic multipotent stem cells, including hematopoietic stem cells (HSC), mesenchymal stem cells (MSCs), and neural stem cells (NSCs), as well as on pluripotent stem cell (PSC) lines.

The fate of stem cells depends on their interactions with the local microenvironment, i.e. the niche. One of Dr. Khaldoyanidi’s research interests is to identify the cells that contribute to the complex structure of the hematopoietic niche in bone marrow. Her laboratory is also studying the non-cellular compartment of the niche, which includes extracellular matrix molecules, chemokines, anaphylotoxins, and cholinergic mediators. Ongoing studies are investigating the molecular mechanisms by which these factors mediate their effects on the fate of stem cells and on the cross-talk between stem cells and the niche.

Multipotent stem cells, or other differentiated cells derived from pluripotent stem cells, are of potential use for tissue regeneration. One current problem is to generate the desired cells in sufficient quantities for transplantation. The critical issue, which has been insufficiently addressed, is to improve the efficiency of PSC differentiation into the desired specific lineage. Dr. Khaldoyanidi’s laboratory is studying how extracellular matrix components, produced by PSCs, regulate the fate of PSCs.

Transplantation of stem cells is necessary for treatment of many pathological conditions. When cells are administered systemically, the efficiency of transplantation depends on the ability of the stem cells to home to the target organ. Dr. Khaldoyanidi’s laboratory has established a new in vitro method, based on a 3-dimesional (3D) flow chamber device, to investigate the effects of the organ-specific microenvironment on stem cell - endothelial cell interactions under physiological shear stress conditions. The device allows the discrete steps of the cell-cell interaction to be studied, including rolling on, adhesion to, and transmigration of the stem cells across an endothelial layer. This approach will contribute to our understanding of the mechanisms that regulate stem cell migration, and may lead to the development of treatments that either enhance or prevent homing of cells into the target organ.


  • 1983 - 1989: Medical State University, Novosibirsk, Russian Federation, M.D. (Pediatrics)
  • 1989 - 1993: Institute of Clinical Immunology, Novosibirsk, Russian Federation, Ph.D. (Immunology/Hematology)
  • 2005 - 2006: The Burnham Institute for Medical Research, Stem Cell Center, sabbatical; La Jolla, California, USA


  • 1993 - 1995: Guest Scientist, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 1995 - 1998: Guest Scientist, Institute for Genetics (IGEN), Karlsruhe Research Center (FZK), Karlsruhe, Germany
  • 1998 - 1999: Postdoctoral Fellow, Laboratory for Hematopoiesis Research, Medical Biology Institute, La Jolla, CA, USA
  • 1999 - 2001: Research Scientist, Department of Vascular Biology, LJIMM, La Jolla, CA, USA
  • 2001 - 2007: Assistant Professor, Department of Vascular Biology, LJIMM, San Diego, CA, USA
  • 2005 - 2007: Director, Stem Cells and Regenerative Medicine Program, LJIMM, San Diego, CA, USA
  • 2007 - Present: Associate Member, Torrey Pines Institute for Molecular Studies, San Diego, CA

Professional Affiliations

  • American Society of Hematology, since 1998
  • International Society of Experimental Hematology, since 2000
  • International Society for Hyaluronan Science, Since 2007
  • International Society for Stem Cell Research, Since 2008

Selected Publications (10 of 42)

  1. Khaldoyanidi, S.K.; Moll, J.; Karakhanova S.S.; Herrlich, P.; Ponta, H. Hyaluronate-enhanced hematopoiesis: Two different receptors trigger the release of interleukin-1beta and interleukin-6 from bone marrow macrophages. Blood (1999), 94(3), 940-949
  2. Khaldoyanidi, S., Karakhanova S., Sleeman, J., Herrlich, P., Ponta, H. CD44 variant specific antibodies trigger hemopoiesis by selective release of cytokines from bone marrow macrophages. Blood, (2002),99(11):3955-3961
  3. Matrosova V, Orlovskaya I, Serobyan N. and Khaldoyanidi S. Hyaluronic acid facilitates recovery of hematopoiesis impaired by 5-fluouracil administration. Stem Cells, 2004;22:544-555
  4. Franz-Josef Mueller, Naira Serobyan, Ingrid U. Schraufstatter, Richard DiScipio, Jeanne F. Loring, Evan Y. Snyder and Sophia K. Khaldoyanidi. Adhesive interactions between human neural stem cells and inflamed human vascular endothelium are mediated by integrins. 2006, Stem Cells, 24(11):2367-72.
  5. Irina Orlovskaya, Ingrid Schraufstatter, Jeanne Loring and Sophia Khaldoyanidi. Hematopoietic differentiation of embryonic stem cells. Methods, 2008; 45:159-167
  6. Sophia Khaldoyanidi. Directing stem cell homing. 2008, Cell Stem Cell, 2:198-200.
  7. Nadezhda Omelyanchuk, Irina A. Orlovskaya, Ingrid U. Schraufstatter and Sophia K. Khaldoyanidi. Key Players in the Gene Networks Guiding ESCs toward Mesoderm. Journal of Stem Cells, 2009; .4(3):147-160
  8. Schraufstatter, I.U., DiScipio, R.G., Zhao, M. and Khaldoyanidi, S.K. C3a and C5a are chemotactic factors for human mesenchymal stem cells, which cause prolonged ERK1/2 phosphorylation. J. Immunol., 2009, 182: 3827-3836.
  9. Ingrid Schraufstatter, Naira Serobyan, Richard DiScipio, Natalia Feofanova, Irina Orlovskaya and Sophia Khaldoyanidi. Hyaluronan stimulates mobilization of mature hematopoietic cells but not hematopoietic progenitors. Journal of Stem Cells, 2009:4(4):191-202.
  10. Ingrid U. Schraufstatter, Naira Serobyan, Jeanne Loring and Sophia K. Khaldoyanidi. Hyaluronan is required for generation of hematopoietic cells during differentiation of human embryonic stem cells. Journal of Stem Cells, 2010, 14:81-91, 2005.

  1. Pending - Device for evaluating in vitro cell migration under flow conditions, and methods of use thereof. United States Patent Application Serial No. 11/395,812. United States Attorney Docket No. 8059-003 PR (filed March 31, 2004)

  • Medical State University, Novosibirsk, Stipend of Excellence 1983-1989
  • Boehrihger Ingelheim, Germany, Guest Scientist Award 1993
  • German Cancer Research Center, Heidelberg, Germany, Guest Scientist Award 1994-1995
  • Forschungszentrum Karlsruhe, Germany, Guest Scientist Award 1995-1998
  • American Society of Hematology, travel Award 1999
  • International Society of Hematology, travel Award 2003
  • International Drug Discovery Science and Technology, Honorary Member, 2004
  • International Society of Hematology, Member of the Month, October 2006


  • Stem Cells
  • British Journal of Haematology
  • International Journal of Biochemistry and Cell Biology
  • International Journal of Biological Macromolecules
  • Journal of Immunological Methods
  • Oncogen
  • PNAS


  • Frontiers in Bioscience
  • Grant reviewer: Universite du Luxemnourg, 2006
  • PhM Research Management Group, 2007
  • NIH, since 2008

Toni Ortiz

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.

Read more

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.

Read more

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.

Read more

Roy Riblet

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.

Read more

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.

Read more