Associate Professor Archives - Sanford Burnham Prebys (2024)

Dr. Sheffler joinedSanford Burnham Prebys in September 2012.

Education

2005-2010: Post-doctoral Training, Vanderbilt University, Nashville, TN Mentor: Jeffrey Conn, PhD
1999-2005: PhD, Case Western Reserve University, Cleveland, OH Mentor: Bryan Roth, MD, PhD

Honors and Recognition

2013 NARSAD Young Investigator Award Brain and Behavior Research Foundation

Related Disease
Alzheimer’s Disease, Huntington’s Disease, Neurodegenerative and Neuromuscular Diseases, Neurological and Psychiatric Disorders, Schizophrenia

Dr. Sheffler joined the Sanford Burnham Prebys faculty in September 2012. Prior to this, he was a Research Assistant Professor at Vanderbilt University in the laboratory of P. Jeffrey Conn (2010-2012), where he also performed post-doctoral work (2006-2010). Dr. Sheffler has over 15 years’ experience in the study of G-protein coupled receptor (GPCR) signaling, assay development, high throughput screening for novel GPCR ligands, cell biology, neuroscience, and pharmacology. His interests are in the complex regulation of GPCRs: their signal transduction, ligand binding, receptor desensitization, and the processes of GPCR internalization and down-regulation. In addition, he has also has a specific interest in both the pharmacology of GPCRs, in general mechanisms of signal transduction, and in the pathogenesis of schizophrenia. During his graduate studies at Case Western Reserve University in the laboratory of Bryan L. Roth, MD, PhD, he discovered the regulation of 5-HT2A serotonin receptor signal transduction by p90 ribosomal S6 kinase (RSK2). During his post-doctoral studies and work as a Research Assistant Professor at Vanderbilt University, he focused on the discovery and characterization of orthosteric and allosteric modulators of GPCRs and led pharmacology efforts characterizing novel M1 muscarinic acetylcholine receptor agonists and antagonists, M1 positive allosteric modulators (PAMs), Glycine Transporter Type 1 (GlyT1) inhibitors, and novel Group II metabotropic glutamate receptor (mGlu) PAMs and NAMs. Dr. Sheffler’s research has resulted in more than 45 journal articles and is a listed inventor on fivepatent applications pertaining to small molecule therapeutics. Dr. Sheffler received a NARSAD Young Investigator Award in 2013 from the Brain and Behavior Research Foundation.

Douglas Sheffler’s Research Report

The metabotropic glutamate receptors (mGlus) are G protein-coupled receptors (GPCRs) that play numerous roles in modulating synaptic transmission and cell excitability. Recent preclinical and clinical studies provide strong evidence that agonists of the group II mGlus, comprised of the mGlu2 and mGlu3 subtypes, may provide a novel approach to treatment of schizophrenia and anxiety disorders. Based on this, there has been a major focus on understanding the roles of these receptors in regulating transmission in forebrain and limbic circuits. However, currently available orthosteric (glutamate site) agonists activate both mGlu2 and mGlu3 and do not provide insight into which subtype is most important for clinical efficacy. Alternatively, recent focus on compounds interacting with less highly conserved allosteric sites has led to advances in subtype selective compound development. Dr. Sheffler and others have discovered and characterized highly selective mGlu2 positive allosteric modulators (PAMs), that have no effect on mGlu3, and these compounds have allowed us to elucidate many of the physiological roles of mGlu2. These PAMs do not activate the receptor directly but act allosterically to potentiate glutamate responses. Dr. Sheffler and collaborators have also discovered group II mGlu negative allosteric modulators (NAMs) and have very recently discovered the first highly selective antagonist of mGlu3. The development of these pharmacological tools provides an opportunity to fully elucidate the roles of these mGlu subtypes. The group II mGlus play important roles in regulating transmission through the hippocampal formation. For example, activation of presynaptic group II mGlus reduces transmission at numerous hippocampal synapses including perforant path-dentate gyrus synapses and the mossy fiber synapse. In contrast, presynaptic group II mGlus are not involved in directly regulating transmission at the Schaffer collateral – CA1 (SC-CA1) synapse. However, we have previously reported extensive studies demonstrating group II mGlu involvement in a novel form of glial-neuronal communication in hippocampal area CA1. When coincidentally activated with β-adrenergic receptors (βARs) in astrocytes, group II mGlus induce a marked potentiation of cAMP responses elicited by activation of βARs. This synergistic increase in glial cAMP accumulation results in the release of adenosine, which activates presynaptic A1 adenosine receptors on neighboring SC terminals and induces a profound depression of transmission at the SC-CA1 synapse. This novel form of glial-neuronal signaling may provide a protective mechanism to reduce the risk of excitotoxicity when there is excessive excitatory drive to the hippocampus, such as during periods of intense or prolonged stress. This potential role has implications relevant for the therapeutic effects of group II mGlu agonists and is consistent with multiple studies suggesting group II mGlu agonists can reduce both acute and long term responses to stress. We have postulated that this effect is mediated by mGlu3 based on heavy expression of mGlu3 in hippocampal astrocytes. However, until now, selective reagents that differentiate between mGlu2 and mGlu3 have not been available to rigorously determine the specific group II mGlu subtype involved. The long term goal of Dr. Sheffler’s research is to establish the relative roles of individual group II mGlu subtypes in mediating glial-neuronal communication and modulating synaptic transmission in the hippocampus using pharmacological, biochemical, and electrophysiological approaches.

Charles Spruck earned his BS in Biology at UCLA and PhD in Molecular Biology at the University of Southern California. He worked as a postdoctoral fellow at The Scripps Research Institute in La Jolla and was recruited to the Sidney Kimmel Cancer Center in San Diego as an Assistant Professor in 2003. He joined Sanford Burnham Prebys in 2010.

Education and Training

2003: Post-doc, The Scripps Research Institute
1986: PhD, University of Southern California
1995; BS, University of California at Los Angeles

Prestigious Funding Awards /Major Collaborative Grants

NIH/NCI DoD BCRP CBCRP TRDRP

Honors and Recognition

ACS Scholar

Related Disease
Breast Cancer, Cancer, Lung Cancer, Molecular Biology

Phenomena or Processes
Cancer Biology, Cancer Epigenetics, Cell Biology, Cell Cycle Progression, Cell Signaling, Genomic Instability, Innate Immunity, Metastasis, Posttranslational Modification, Proteolytic Pathways

Research Models
Cultured Cell Lines, Human Cell Lines, Mouse, Mouse Cell Lines

Techniques and Technologies
Cell Biology, Drug Discovery, Gene Knockout (Complete and Conditional), In vivo Modeling

Dr. Spruck’s laboratory is focused on developing new, effective, and non-toxic treatments for patients with advanced cancers. The lab focuses on defining the molecular networks that regulate cancer cell division and drive metastasis progression. Recent studies have focused on viral mimicry as a therapeutic approach in cancer, which involves the activation of dormant endogenous retroviruses and retrotransposons in cancer cells to enhance immunogenicity and the effectiveness of immune checkpoint blockade immunotherapy and DNA damaging therapies. The laboratory utilizes various biochemical and molecular approaches, CRISPR gene editing, and animal models of cancer. An emphasis is on studies of breast, lung, prostate, and brain tumors.

Charles Spruck’s Research Report

Developing viral mimicry therapeutic approaches for cancer:Approximately 45% of the human genome is composed of repetitive elements (REs), including endogenous retroviruses and retrotransposons, that are normally transcriptionally silenced in somatic cells. Recent studies suggest that the transcriptional awakening of ERVs/retrotransposons beyond a threshold level of tolerance in cancer cells induces antiviral responses that can enhance the efficacy of certain therapies, including immunotherapy. We recently discovered a novel epigenetic regulatory pathway, FBXO44/SUV39H1, that is essential for ERV/retrotransposon silencing in cancer cells. Preclinical studies showed that FBXO44/SUV39H1 inactivation induces viral mimicry in cancer cells, leading to increased immunogenicity, decreased tumorigenicity, and enhanced the efficacy of immune checkpoint blockade therapy. We are currently exploring therapeutic approaches to target this pathway, and others like it, to prevent tumor growth and enhance immunotherapy response. We are also exploring the role of reactivated REs in human diseases.

Targeting metastatic tumors:Metastasis is a major cause of mortality in cancer. Through genomic screens and biochemical studies, we are identifying novel molecular pathways that drive cancer cell motility, invasion, and metastasis. Recently, we identified a novel molecular axis, FBXO7/EYA2-SCF(FBXW7), that promotes cancer cell motility and cancer stem cell self-renewal and suppresses cancer cell immunogenicity. Targeting this axis prevented metastasis progression, reduced the cancer stem cell population, and stimulated anti-tumor immune responses in preclinical mouse breast cancer models.

Emerlingreceived her B.A.from the University of California Santa Cruz and her PhD in molecular and cellular biology from Northwestern University. Emerling did her postdoctoral training at Harvard Medical School. She then became an Instructorof Cancer Biology in Medicine at Weill Cornell Medical College in New York City, where she continued her research on lipid kinase signaling and cancer metabolism.In August 2016,Brooke joined the faculty atSBPMedical Discovery Instituteas an Assistant Professor in theCancer Metabolism and Signaling Networks Program.

Funding Awards and Collaborative Grants

Breast Cancer Research Foundation – AACR Career Development Award for Translational Breast Cancer Research
Mary Kay Foundation Innovative Translational Grant Award
Department of Defense Breast Research Program Breakthrough Award

Honors and Recognition

2014: NextGen Star – AACR Early-Career Speaker Award
2013-2016: Mastercard Ajay Banga Scientist Award
2013: AACR –Aflac Travel Fellowship Award

Related Disease
Breast Cancer, Cancer

Phenomena or Processes
Cancer Biology, Cancer Metabolism, Cell Signaling, Metabolic Processes, Signal Transduction

Research in the Emerling Lab is focused on understanding key signaling and metabolic pathways involved in the regulation of cellular function under pathological conditions such as cancer. Our research program centers around dissecting the roles of the family of non-canonical phosphatidylinositol kinases, called the phosphatidylinositol-5-phosphate 4-kinases (PI5P4Ks), in cancer metabolism using a multi-disciplinary approach integrating human, mouse, and worm models. Currently, a major research project in the Emerling Lab is determining the role of the PI5P4Ks in p53 mutant cancers, especially the triple-negative breast cancer subgroup where targeted therapies have not been effective.

Dr. Dong received his Biology Bachelor of Science degree in 1996 from the University of California, Irvine, where he was involved in molecular evolution and limb regeneration research. He earned his PhD in Cell and Molecular Biology at the University of Wisconsin, Madison in 2002, investigating cell/tissue identity master regulatory genes. His postdoctoral research at the University of California, San Francisco was focused on developmental genetics of the liver and pancreas. Dr. Dong was recruited as an Assistant Professor to Sanford Burnham Prebys Medical Discovery Institute in 2008. He is a recipient of the NIH Director’s New Innovator Award Award and the W. M. Keck Foundation Award, which funds the development ofin vivolineage reprogramming technologies to generate replacement cells and organs directly within a living vertebrate.

Education

BS, Biology, University of California, Irvine
PhD, Cell & Molecular Biology, University of Wisconsin, Madison
Postdoctoral Fellow, Genetics and Development, University of California, San Francisco

Related Disease
Alagille Syndrome, Congenital Diseases, Degenerative Diseases, Liver Diseases, Monogenic Diabetes, Pancreas Diseases, Type 1 Diabetes, Type 2 Diabetes

Phenomena or Processes
Aging, Human Evolution, Organogenesis, Regenerative Medicine

Anatomical Systems and Sites
Developmental Biology, Synthetic Cell Biology

Techniques and Technologies
Developmental Genetics, Disease Genetics

Our objective is to uncover fundamental insight into basic and biomedical science through rigorous investigation of the genetic mechanisms governing organogenesis and diseases. We have discovered multiple genes critical for generating liver and pancreas cells and have created novel animal models for diseases such as diabetes and Alagille Syndrome. These unique experimental models have been yielded mechanistic insight and potential new therapeutic avenues. Further, we have demonstrated for the first time that a cell’s identity can be reprogrammed to convert into a completely unrelated lineage, without their removal from the body (in vivo) and without passage through a stem cell intermediate. Thisin vivolineage reprogramming breakthrough may lead to a vast new and safer source of replacement cells for degenerative diseases and injuries. Ultimately, we aim to develop genetic technologies to improve human health and advance human biology.

Dr. Ani Deshpande’s most recent position was as an Instructor with Dr. Scott Armstrong at the Memorial Sloan Kettering Cancer Center and the Children’s Hospital Boston/Harvard Medical School. He completed his PhD in Human Biology from the Ludwig Maximillians University in Munich. Dr. Deshpande’s research revolves around studying difficult-to-cure leukemias through the use of mouse models, genomic and epigenomic studies.

Funding Awards and Collaborative Grants

Ongoing Research Support R00 phase (number in process) Deshpande (PI) 10/0/14-present NIH/NCI – K99/R00 Howard Temin Pathway to Independence Award Role: PI (75% effort) Completed Research Support K99 CA154880 Deshpande (PI) 07/15/11-09/30/14 NIH/NCI – K99/R00 Howard Temin Pathway to Independence Award Role: Post-doctoral fellow/PI

Honors and Recognition

2014: American Society of Hematology Scholar Award (ASH Junior Faculty Scholar Award)
2013: Alex’s Lemonade Stand Foundation Travel Award for the FASEB Hematological Malignancies Meeting in Vermont, VA
2013: Abstract Achievement Award, American Society of Hematology Annual Meeting, New Orleans
2012: Abstract Achievement Award, American Society of Hematology Annual Meeting, Atlanta
2008: ASH Travel Award: 50th Annual Meeting, American Society of Hematology (ASH) San Diego
2008: The New York Stem Cell Foundation (NYSCF) Travel Grant, International Society of Stem Cell Research (ISSCR), Philadelphia
2007: The George Brecher New Investigator Award (postdoctoral) of the International Society of Experimental Hematology, Hamburg, Germany
2007: Doctoral prize of the German Society of Hematology and Oncology (Annual prize for the best doctoral thesis in hematology-oncology in Germany)
2007: The Doctoral Prize of the Helmholtz Centre, Munich for the Best Doctoral Thesis 2006, Munich, Germany
2007: Best Poster Award (2nd Prize): 36th Annual Scientific Meeting, International Society for Experimental Hematology (ISEH) Hamburg
2007: Travel Award: 36th Annual Scientific Meeting, International Society for Experimental Hematology (ISEH) Hamburg
2006: Summa Cum Laude Ludwigs Maximililans University, Munich, Germany
2005: ISEH Travel Grant: 34th Annual Scientific Meeting, International Society for Experimental Hematology (ISEH) Glasgow
2004: ISEH Travel Grant: 33rd Annual Scientific Meeting, International Society for Experimental Hematology (ISEH) New Orleans
2003: ASH Travel Award: 45th Annual Meeting, American Society of Hematology (ASH) San Diego

Related Disease
Cancer, Leukemia/Lymphoma

One of the core interests of the lab is to understand regulation of key developmental processes that are important for normal stem cells and are frequently misregulated in human cancer. We are currently investigating genetic and epigenetic abnormalities in Acute Myeloid Leukemia (AML) using mouse models, gene targeting and genome-scale approaches. Our overarching goal is to uncover therapeutic nodes of intervention in human leukemia.

Available Positions in the Deshpande Lab

We are seeking exceptional candidates with broad interests/expertise in cancer epigenetics and stem cell biology at the level of postdoctoral fellows, graduate students and undergraduates.

• Graduate students
  Applicants interested in graduate positions should send their applications to theSanfordBurnham Prebys Medical Discovery Institute Graduate School for Biomedical Sciences. The application period opens in the fall.
• Undergraduate students
  Please contact Dr. Deshpande via emailadeshpande@SBPdiscovery.org.

Ani Deshpande’s Research Report

Dr. D’Angelo earned his BS and MS degrees in chemistry at the University of Cordoba, Argentina, and his PhD in biochemistry and molecular biology from University of Buenos Aires. He then trained as a postdoctoral fellow in cell biology at The Salk and the Scripps Research Institute in San Diego. In 2011, Dr. D’Angelo was appointed as an Assistant Professor of the Biochemistry and Biophysics department and a Principal Investigator of the Cardiovascular Research Institute at the University of California San Francisco. In 2012, he was named Scholar of the Pew Charitable Trust. Dr. D’Angelo was recruited the to the Development, Aging and Regenerative Program at Sanford Burnham Prebys in October 2014.

Funding Awards and Collaborative Grants

Pew Charitable Trust Scholar in Biomedical Sciences

Related Disease
Aging-Related Diseases

Nuclear pore complexes (NPCs) are multiprotein channels that penetrate the nuclear envelope and act as the gatekeepers of the genome. NPCs work together with nuclear transport receptors to ferry molecules in and out of the nucleus. They also regulate multiple cellular processes such as gene expression, chromatin organization, and RNA processing in a transport independent manner. In recent years, our lab and others identified that cells can change the configuration of nuclear pore complexes to modulate specific cellular processes, such as T cell homeostasis and activation, muscle differentiation, tumor development and metastasis.

Because of the essential function of nuclear pore complexes in cell survival, proliferation and differentiation, it is not surprising that changes in the nuclear transport machinery have long been observed in cancer cells. Yet, how most of these alterations contribute to cell transformation and tumor development is poorly understood.

Our laboratory is working to:

• Establish how alterations in the nuclear transport machinery contribute to cancer development and progression
• Dissect the role of nuclear pore complexes in the regulation of immune cell function
• Identify, validate, and modulate new therapeutic targets for cancer and immune disorders

Our long-term goal is to develop novel therapies targeting the cellular nuclear transport machinery.

Dr. Colas earned his PhD from the Universite Pierre et Marie Curie, Paris, France.

Funding Awards and Collaborative Grants

2011-2013: American Heart Association Post-Doctoral Fellowship
2011: Best Talk Award (Development & Aging Post-Doctoral Retreat, SBP)
2010-2011: California Institute for Regenerative Medicine Post-Doctoral Fellowship
2006-2007: French Myopathy Association PhD Fellowship
2003-2006: Ministry of French Research PhD Fellowship
2000-2001: Erasmus Undergraduate Fellowship

Related Disease
Cardiomyopathies, Cardiovascular Diseases, Heart Disease

Phenomena or Processes
Cardiovascular Biology, Cell Biology, Development and Differentiation, Embryogenesis, Embryonic/Pluripotent Stem Cells, Regenerative Biology, RNA-Based Gene Regulation, Transcription Factors

Our laboratory focuses on the identification and reconstruction of novel regulatory pathways controlling the determination and the acquisition of cardiovascular cell fates in humans. To that end, our team has developed a unique set of cell-based assays suitable for high-throughput functional screening, which enables the implementation of unbiased and systematic experimental approaches with unprecedented exploratory power. Our goal is to leverage generated knowledge to produce better cardiomyocytes to model cardiac diseases in-a-dish as well as to devise innovative cardiac regenerative strategies. In parallel, our lab is also dedicated to identify and develop new drugs promoting cardiac regeneration and/or helping preserving heart function after injury.

Lukas Chavez is an Associate Professor at the Sanford Burnham Prebys. He is also the Director of the Clayes Research Center for Neuro-Oncology at the Institute for Genomic Medicine at the Rady Children’s Hospital, San Diego. In this role, he works with a team of physicians and scientists to capture genomic, transcriptomic, epigenetic and functional data from pediatric brain tumor patients, and uses this information to improve diagnosis and treatment. His research interests focus on structural variants as well as circular extrachromosomal DNA (ecDNA) in childhood cancers. These extrachromosomal DNA circles are frequently found in highly aggressive solid tumors and represent a new target for improved therapeutic approaches.

Education

2010: PhD, Free University, Berlin

Honors and Recognition

2020: St. Baldrick’s Scholar Award, St. Baldrick’s Foundation
2019: Award of Excellence in Pediatric Neuro-Oncology, Society of Neuro-Oncology
2012–2015: Feodor-Lynen Fellowship for Postdoctoral Researchers, Alexander-von-Humboldt Foundation

Related Disease
Brain Cancer, Cancer

Phenomena or Processes
Cancer Biology, Cancer Epigenetics, Chromosome Dynamics, Combinatorial Therapies, Gene Regulation, Genomic Instability, Oncogenes, Transcriptional Regulation

Anatomical Systems and Sites
Brain

Research Models
Clinical and Transitional Research, Computational Modeling, Cultured Cell Lines, Human, Human Cell Lines, Mouse

Techniques and Technologies
Bioinformatics, Cell Biology, Computational Biology, Computational Modeling, Gene Expression, Gene Silencing, Genomics, Single Nucleotide Polymorphisms (SNPs)

Related Disease
Cancer

My lab studies the genetic mutations that drive cancer. I am a geneticist by training, and I am passionate about finding the hidden drivers of cancer. As a research community, we have made tremendous progress in the last few decades in understanding the nature of the beast, but now is the time to translate those knowledge to actionable interventions. A riveting idea that has excited us for sometime is to illuminate the genetic mutations which act as life line to many cancers. This would expose their Achilles heel that we can exploit in near future to develop new forms of treatment. That is what my lab’s work is focused on. We have identified and characterized several key mutations that we have shown as proof of concept can be targeted in as much as 30% of all cancers. The focus of the lab is now to carry out experiments that will allow us to develop this work beyond the proof of concept, ideally to successful clinical trials.