Labs interested in BS/MS students

With BISP 199 availabilities


Anthony J. O'Donoghue

Skaggs School of Pharmacy

ajodonoghue@ucsd.edu

The O’Donoghue lab at the Skaggs School of Pharmacy and Pharmaceutical Sciences are interested in detecting and characterizing proteolytic enzymes (proteases) that are involved in human diseases. In particular, we are interested in understanding the role of these enzymes in cancer. Our research utilizes a mass spectrometry based platform technology to uncover the global proteolytic activity in biological samples such plasma, urine and cancer cells secretions.

We are looking for a BS/MS student that is interested in developing a diagnostic assay for early stage detection of bladder cancer. The research will involve extensive collaboration with urology clinicians at UCSD Jacobs Medical Center.

The Lab Environment

The O’Donoghue lab is located on the 4th floor of Skaggs School of Pharmacy. There is 1 post-doc, 2 PhD students, 3 Masters students and 3 undergraduate students currently in the lab.

Techniques that will be learned include:

Fluorescent protease assays, mass spectrometry, proteomics, cell culture, ELISA.

Must have a strong desire and commitment to perform scientific research in cancer. Must have an understanding of biochemistry. Prior lab experience is a plus but not essential.

Jean Y. J. Wang

Department of Medicine

jywang@ucsd.edu

Title of Project: Investigation of Cell Death Response to Cancer Drugs


Synopsis: We are interested in understanding the functions of PUMA/BBC3 (project 1) and FEN1 (project 2) in the death response of cancer cells to conventional as well as novel cancer drugs. Students will be under the direct supervision of Professor Wang to design, conduct and interpret experiments that use cell biology, molecular biology, biochemistry and genetics approaches. Specifically, students will learn basic as well as advanced techniques, including CRISPR/CAS9-mediated gene editing.

GPA > 3.0

Coursework in Molecular Biology (BIMM100) and Cell Biology (BICD110) required.

Coursework in Biochemical Techniques (BIBC103) and Recombinant DNA Techniques (BIMM101) preferred.

Previous experiences in cell culture, western blotting and PCR preferred.

Carrie McDonald

Center for Multimodal Imaging and Genetics (CMIG)

camcdonald@ucsd.edu

Our lab uses advanced, quantitative neuroimaging and genomic data to predict response to therapy and surgical outcomes in patients with refractory epilepsy and brain tumors.  We are seeking an upper-level student with a strong background in neuro-anatomy to help with several imaging-related projects, including:

  1. Radiogenomics of low-grade gliomas
  2. Prediction of cognitive outcomes and white matter changes in patients with brain tumors undergoing radiotherapy 3. Using deep learning to predict true progression versus pseudo-progression in patients with malignant gliomas 4.  Multimodal imaging for the prediction of cognitive and seizure outcomes following different surgical procedures

Primary responsibilities will include managing a RedCap database of imaging and clinical information on patients with brain tumors or epilepsy, assisting with the creating of regions-of-interest on MRI scans, and for students with a programming background, working with a biomedical engineer to analyze imaging data.  Students will have exposure to a range of clinicians and researchers, including engineers, neuroradiologists, neuropsychologists, and radiation oncologists through regular lab meetings.

Must be able to commit to 10 hours per week, 1-2 days per week for at least 1-year.  Experience with patient-oriented research, neuro-anatomy, and/or programming are preferred.  We are particularly interested in students who have a long-term goal of conducting clinical research or aspire to develop their own project within our lab after the initial year. 

Jack Bui

Medical Center Cancer Center

jbui@mail.ucsd.edu

  1. Role of IFN in promoting cancer stem cells
  2. Role of the cancercell in producing cytokines and initiating immune responses
  3. Role of cell-cell fusion in cancer progression
  4. Role of the cytokine IL-17D in antitumor and antiviral immunity
Need to have cell culture experience

Stephen A. Spector

Division of Infectious Disease

saspector@ucsd.edu

The Dr. Stephen Spector laboratory has used molecular and Immunologic approaches to study host-virus interactions of human cytomegalovirus (CMV) and human immunodeficiency virus type-1 (HIV-1) with a particular emphasis developing novel approaches for the detection, treatment and eradication of persistent viruses. Current CMV related research is examining the role of CMV in endothelial cell inflammation and the development of cardiovascular diseases. The laboratory has been involved with HIV/AIDS research since the beginning of the epidemic. Current research examines HIV pathogenesis with a particular emphasis on host-virus interactions, and the associations of host genetic variants on HIV diseases progression and HIV-related diseases including CNS impairment in children and adults. The laboratory has also identified specific host genetic variants that are associated with mother-to-child transmission, HIV disease progression, and antiretroviral pharmacokinetics and adverse effects. The laboratory’s interest in the identification of host factors that affect HIV pathogenesis and neurocognitive impairment led to the novel finding that during permissive infection, HIV down-regulates autophagy to promote its own replication, and the induction of autophagy (using mTOR inhibitors as well as vitamin D3) inhibits HIV replication. Most recently, Dr. Spector’s laboratory has discovered that a Na+/K+-ATPase dependent mechanism of autophagy, termed autosis, has the potential to preferentially kill HIV persistently infected cells. This research has led to him to examine the association of host factors that control HIV replication with the goal of identifying novel strategies to eradicate HIV in order to cure persons infected with HIV.

What type of activities will you assign to your research assistant?

FMP students will work closely with a postdoctoral fellow or Research Scientist in the laboratory. Students will learn how to grow cells in culture and basic molecular biology techniques including extraction of DNA, RNA and proteins, PCR, western blots, immunostaining, etc. It is hoped that by end of the first semester students will have learned sufficient techniques to begin working on their own research project under the guidance of Dr. Spector and their direct laboratory research mentor. Many students have gone on to complete a Master’s thesis in the laboratory as part of the BS/MS program before entering medical school or pharmacy school.

Students must have GPA 3.5 or higher to be considered for the lab.

Prashant Mali

Bioengineering

pmali@ucsd.edu

We have several projects in the area of CRISPR-Cas based genome engineering that we are actively seeking motivated researchers for. Also here is the lab website for the students to further explore: http://mali.ucsd.edu

Frank L. Powell

Division of Physiology

fpowell@ucsd.edu

Our laboratory focuses on determining the genetic and molecular signals for physiological mechanism of neural plasticity and ventilatory acclimatization to chronic hypoxia. We study healthy people from sea level and adapted to high altitude in the Andes and Tibet, as well as patients with chronic lung disease and animal models, including transgenic mice. These studies are relevant to lung disease causing chronic sustained hypoxia and chronic mountain sickness, and sleep apnea that causes intermittent hypoxia. We are especially interested in mechanisms of susceptibility and tolerance to chronic hypoxia in microcircuits that control breathing in the central nervous system.

Our recent physiology experiments study:

  • The effects of HIF-1α versus HIF-2α in neurons versus glia for plasticity in the CNS with chronic hypoxia.
  • The role of glia and inflammatory signals in acclimatization to chronic hypoxia.
  • Plasticity in the control of breathing in patients with chronic hypoxemia from lung disease.

We study the problem at multiple levels in animal models with experimental approaches including:

  • measuring ventilatory responses, metabolism and respiratory muscle activity in conscious, freely moving, instrumented rats and transgenic mice,

  • temporally and spatially specific conditional gene deletion using loxP-Cre strategies in transgenic mice,

  • neurophysiological studies of chemoreceptor reflexes in anesthetized rats and mice

  • in vivo and confocal fluorescent imaging, immunohistochemistry and molecular biological measures of signals for neural plasticity.


We also study the genetic determinants of individual variation in the hypoxic ventilatory response, including ADAPTATIONS in human populations native to high altitude in Peru and Tibet. In addition to measuring ventilatory responses, respiratory gas exchange and functional MRI in humans during acclimatization to hypoxia at high altitude, genetic studies include:

  • Shared and unique genetic adaptations and physiological traits exhibited in different highland populations.
  • The effects of hemoglobin concentration on oxygen transport, sleep, and gene expression at high altitude.
  • The effects of sleep treatments at high altitude.
  • The role of HMOX in regulating hemoglobin concentration and ventilatory control in highland populations.

For more information please see Frank Powell and Tatum Simonson’s on the  Division of Physiology website (under “People” tab) or the Center for Physiological Genomics of Low Oxygen (CPGLO) website .

Course in physiology preferred

Allen F. Ryan

Departments of Surgery/Otolaryngology and Neurosciences

aryan@ucsd.edu

My laboratory performs research in the field of otology, specializing in the characterization, treatment and prevention of hearing loss.  This includes studies on the molecular mechanisms of damage to sensory cells and neurons in the inner ear, with the aim of identify potential therapies.  We also use screen compound libraries using cochlear tissue from transgenic mice in which the inner ear sensory cells selectively express GFP.  We are performing a human genome-wide association study to identify genes associated with tinnitus and hearing loss.   In addition to our neuroscience research, we study the molecular substrates of pathogenesis and recovery in otitis media (ear infections), using gene knockout models and single-cell transcriptomics to identify inflammatory and innate immune defense genes that are active in this disorder.  Finally, we investigate novel methods for drug delivery to the middle and inner ears, including a newly discovered mechanism that actively transports particles across the intact tympanic membrane.

Alessandra Franco

Pediatrics

alfranco@ucsd.edu

Human Immunology laboratory with emphasis in T cell recognition and immunotherapy design. Current focus is the role of natural regulatory T cells that recognize the heavy constant region of immunoglobulins in down-regulating inflammation.

 

Techniques involved: flow cytometry, culture of primary cells, ELISA.

Maike Sander

Sanford Consortium for Regenerative Medicine

masander@ucsd.edu

Diabetes is a complex disease characterized by the inability to control blood glucose levels. The hormone insulin is essential for blood glucose regulation, and insufficient insulin production underlies both type 1 and type 2 diabetes. Insulin is secreted into the bloodstream by pancreatic beta cells. In diabetes, beta cells fail to produce sufficient insulin due to either their destruction by the immune system (in type 1 diabetes) or an excessive demand for insulin exceeding beta cell functional capacity (in type 2 diabetes). Therefore, strategies to augment insulin production by improving beta cell function or increasing beta cell numbers have potential to restore blood glucose control in either type of diabetes.

To identify novel strategies for enhancing beta cell mass and function, we have sought to better understand how these processes normally occur during adaptation of beta cells to metabolic challenges. Prolonged changes in energy balance alter insulin demand and evoke coordinated adjustments to the number and function of beta cells. Thus, our studies have converged upon the roles of metabolic signaling in the adaptive processes of (1) beta cell proliferation and (2) enhancement of the insulin secretory response. Thus far, we have uncovered novel regulators of both beta cell replication as well as insulin secretion.

The Sander laboratory studies beta cell biology by employing genetic mouse models, animal physiology, genomics, and metabolomics. We have interrogated the roles of pathways of interest in beta cell adaptation to metabolic challenges using mouse models whose beta cells have been challenged through dietary, genetic, or pharmacological interventions. Future studies will assess the potential therapeutic value of modulating pathways of interest by investigating the effects in mouse models of diabetes. Furthermore, we will utilize genomic studies to determine the molecular mechanisms linking gene regulation to beta cell phenotypes (e.g. proliferation and insulin secretion). Through integration of our lab’s expertise in beta cell biology and genomics, we take a systems level approach to investigate the effect of gene perturbations on beta cell function.

Students will have the opportunity to play an important role in this exciting project. The student will work closely with scientists in the lab to generate mouse models of diabetes and monitor disease progression. Students will characterize various aspects of beta cell biology in these models, including determination of insulin secretion, monitoring beta cell proliferation, performing genomic studies, and assessing responsiveness to nutritional or signal transduction pathways. In parallel with mouse studies, culture models that mimic the diabetic environment will be utilized, enabling the application of cell culture tools such as CRISPR-Cas9 as well as validation in human beta cells. Through this experience, the student will learn techniques in animal physiology, endocrinology, molecular biology, and next generation sequencing. If interested, students will have the opportunity to interact with bioinformaticians to interrogate next generation sequencing data.

Previous laboratory and rodent handling experience is highly advantageous.

Nunzio Bottini

nbottini@ucsd.edu

Stephanie Stanford

ststanford@ucsd.edu

Clinical and Translational Research Institute

We study protein tyrosine phosphatases, enzymes that play an important role in signal transduction and are critical for numerous cellular processes in health and disease. We have projects available to biochemically and biophysically characterize protein tyrosine phosphatases that are involved in the immune response and play a role in autoimmunity and cancer immunosurveillance.

Jianhua Shao

Pediatrics

jishao@ucsd.edu

Our research focuses on obesity, gestational diabetes and intrauterine metabolism.

Motivated students with a desire to pursue a medical or biomedical research career.

Dong Wang

Skaggs School of Pharmacy and Pharmaceutical Sciences

dongwang@ucsd.edu

Potential projects are:

  1. In vitro transcription studies on synthetic DNA
  2. Structure and function studies of transcription-coupled repair
  3. Structure and function studies of chromatin remodeling

Shauna Yuan

Department of Neurosciences

shyuan@ucsd.edu

Astrocytes are support cells in the brain.  Although astrocytes harbor pathological hyperphosphorylated tau and neurofibrillary tangles, hallmarks in neurodegenerative diseases, how they contribute to disease is not clear.  This project is to investigate tau phosphorylation and tau splicing in human astrocytes.  We have preliminary results, which show that tau phosphorylation and tau splicing in astrocytes are significantly different from neurons, suggesting that the mechanisms regulating tau protein modification is different in astrocytes than neurons.  These important questions will be answered by comparing human astrocytes and neurons derived from human induced pluripotent stem cells.  The student will learn to cultures human astrocytes and neurons, quantitative PCR, immunofluorescent staining, and Western blot.  

Hollis Cline

Department of Neuroscience

cline@scripps.edu

Our research is focused on understanding the mechanisms by which experience controls the development of the brain. The lab addresses this fundamental neuroscience question by examining the development of the visual system in Xenopus tadpoles, which is well known for its experience-dependent plasticity. Using in vivo imaging, electrophysiology, behavioral assays, and manipulation of gene expression, we have discovered that neuronal activity regulates the development of the visual system through a variety of mechanisms, including changes in neuronal structure, synaptic strength, synaptogenesis, and gene expression.

 The tadpole visual system is highly dynamic and We have shown that animals can recover visually-guided behaviors after brain injury. We are investigating the response to injury.

We have 3 types of projects. 1: students will use the tadpole system to study mechanisms controlling recovery from brain injury. Students will be exposed to methods including whole-brain electroporation, in vivo imaging, immunofluorescence, molecular biology, biochemistry, tadpole husbandry, and general lab techniques. They will learn animal behavior assays and analysis as well. 2: students will participate in a project on computational bioinformatic analysis of RNA Seq data from Xenopus brain tissue. 3: students will participate in a project investigating visual response properties using electrophysiological or imaging methods and quantitative data analysis. Students will be part of a dynamic group of scientists seeking to understand the fundamental aspects of cellular neuroscience using modern molecular techniques and state of the art technology.

Tariq Rana

Pediatrics and Genetics

trana@ucsd.edu

Research opportunities are available in a multidisciplinary laboratory studying fundamental questions in Immunobiology and RNA biology. Ongoing projects include: (1) Bioinformatics and systems medicine using HT genome sequencing of blood cells from cancer and AIDS patients. (2) CRISPR-Cas9 applications in immune system engineering. (3) Developing new approaches for cancer immunotherapies.

Additional Info: Under supervision of a postdoctoral fellow or a staff scientist, you will be exposed to: bioinformatics analyses of large genomics data sets, culturing and differentiation of stem cells, drug discovery, viral transduction, RNA and DNA isolation, PCR and gel electrophoresis, transfection, western blot, in vivo and in vitro cancer models, and lab maintenance. For additional information about projects and publications, see http://biomedsci-db.ucsd.edu/faculty_detail?f=249

Skills and Qualifications: Must have a strong desire and commitment to perform scientific research in human disease mechanisms. Must have an understanding of biochemistry, bioinformatics, chemistry, cell biology, or molecular biology. Prior lab experience is a plus.

Documents to Submit: Resume, Cover Letter, Unofficial Transcript

Send Materials to: Rana Lab.  trana@ucsd.edu

Huilin Zhou

Department of Cellular and Molecular Medicine

huzhou@ucsd.edu

Information about the Huilin Zhou Lab Projects can be found at:  https://www.huilinzhoulab.org/  

We prefer interested students that meet the minimum BS/MS GPA requirements

Karl Willert

Cellular and Molecular Medicine

kwillert@ucsd.edu

The Big Picture: A central question in developmental biology is how cells in an embryo become different from one another. Many years of research have shown cellular diversity arises as a consequence of cells interacting with their immediate environment and receiving instructive signals from neighboring cells and the extracellular matrix. Like the developing embryo, human pluripotent stem cells (hPSC) maintained in the laboratory communicate with one another using signaling molecules and thereby either maintain their pluripotent state or assume new properties. Recreating the cellular microenvironments and reiterating the developmental signaling events by controlling the dosage, timing, and combinations of developmental signaling molecules is of critical importance in establishing protocols for reproducible generation, expansion and lineage specific differentiation of hPSCs.

What We Study: In my laboratory we study a major class of signaling proteins encoded by the WNT gene family, which exerts potent effects on stem and progenitor cells. Despite a vast body of research on the role and mode of action of WNTs in developmental biology, how these signaling proteins control cell fate choices of hPSC is poorly understood.  A long-term goal of the lab is to develop methods and protocols to specifically manipulate stem cell fate with WNT proteins, thereby providing the means to derive and isolate mature cell populations. 

The Lab Environment: The Willert laboratory is located in the Sanford Consortium for Regenerative Medicine (SCRM), where over 25 PIs with stem cell interest have established their research programs. At present, 8 full time scientists work in the Willert lab: one post-doc, two Ph.D. students, two Masters student, and 3 lab technicians. In addition, two undergraduate students work in the lab on a part-time basis. We have weekly lab meetings at which individual lab members present their research progress and future plans. SCRM offers a highly interactive environment with several scientific seminar series.

Potential Projects:

  1. Protein engineering. WNT proteins are potent stem cell factors that, depending on cellular context, promote self-renewal or differentiation. However, WNT proteins are difficult to isolate as bioactive molecules, which has limited their usefulness in cell and tissue engineering. We have developed approaches to overcome these obstacles by engineering novel WNT-like proteins. A student working on this project will learn how to purify proteins and test activities on hPSCs.
  2. WNT signaling in blood development. Blood stem cells are widely used in the clinic to treat a variety of incurable diseases, however, supplies of patient-matched blood stem cells are limited. Developing protocols to generate blood stem cells from hPSCs would be revolutionary in regenerative medicine. Using zebrafish as a model system we found that a specific Wnt gene is required for proper blood stem cell development (Grainger et al. Cell Reports, 2016). Furthermore, we found that this WNT requirement is conserved in humans (in press). A student working on this project will have the opportunity to work with human pluripotent stem cells and differentiate them towards blood lineages.
  3. The role of FZD7-WNT signaling in stem cells and cancer. We have found that the WNT receptor FZD7 is required for maintenance of hPSCs in a pluripotent state (Fernandez et al. PNAS, 2014). In the course of these studies, we developed an antibody to FZD7, which inhibits WNT signaling through this receptor. FZD7 has also been found to have important roles in cancer, and our antibody represents a unique opportunity to block cancer growth. An intern working on this project will have the opportunity to work with human pluripotent stem cells and human cancer cells and test the hypothesis that disruption of WNT-FZD7 signaling blocks stem and cancer cell growth.

The only requirements I have is that a student can commit a minimum of 1 year (preferably longer) to my lab and that they are interested in and excited by research.

Chengbiao Wu

Neuroscience

chw049@ucsd.edu

1. Mechanisms of cortical-striatal atrophy in HD

We focus on the investigation of axonal trafficking and signaling of BDNF in mouse models of Huntington's disease (HD). Our studies have demonstrated that defective axonal transport of BDNF in cortical neurons contributes significantly to striatal atrophy in HD. More importantly, we have shown that TRiC chaperonin has a protective role against axonal toxicity induced by mutant Huntingtin

2. Axonal dysfunctions in Tauopathies

Tau is a microtubule associated protein (MAP). Hyper-phosphorylation or mutations in many sites on Tau are believed to contribute to its significant neurotoxicity. Using human neurons differentiated from iPS cells derived from human Tauopathy patients, we are interested in understanding: 1:  how pathogenic Tau species affects axonal transport of neurotrophic factors such as BDNF; and 2: if and how pathogenic Tau can spread via axons from neurons to neurons, or from gila to neurons, or vice versa

3. Molecular and cellular mechanisms of CMT2B peripheral sensory neuropathy

Charcot-Marie-Tooth disease type 2B (CMT2B) is caused by autosomal dominant mis-sense mutations of the small GTPase Rab7 in people. We will investigate, both in vivo and in vitro, the hypothesis that CMT2B Rab7 mutation(s) causes hyper-activation of Rab7 and disrupts axonal trafficking and signaling of neurotrophic factors, leading to axonal degeneration of peripheral sensory neurons. The hypothesis is built on our in vitro studies published previously (Zhang et al., 2013, J Neurosci. 33:7451-62); and our strong preliminary in vivo results of the first ever mouse model of CMT2B, demonstrating sensory dysfunction in a knockin mouse model. In addition, we have obtained human CMT2B fibroblasts together with their control cells.  We plan to convert these cells into sensory neurons using the recently developed technologies by our collaborator Dr. K Baldwin at TSRI. By carefully examining the animal model, studying the cellular and molecular mechanisms in both animal neurons and human neurons, we will gain significant insights into the pathogenic mechanism(s) of CMT2B towards potential therapies for this debilitating disease.

4.  Molecular and cellular mechanisms of HSAN V

Hereditary Sensory and Autonomic Neuropathy V (HSAN V) is associated with a naturally occurred autosomal recessive mutation in NGF, discovered in a Swedish family whose patients suffer from selective loss of sensation to deep pain.  In this project, we will investigate and characterize the signaling mechanisms of this novel NGF mutant both in vitro and in vivo.  We will study how the mutation alters NGF’s ability to signal through TrkA and/or p75.  Our preliminary studies support the hypothesis that the mutant NGF retains its ability to signal through TrkA while no longer engaging the p75-mediated signaling pathways. We are actively exploring the potential use of this novel NGF mutant for treating peripheral sensory neuronal degeneration such as diabetic neuropathy, CHEMO- and HIV-induced neuropathy.

Asa Gustafsson

Skaggs School of Pharmacy and Pharmaceutical Sciences

abgustafsson@ucsd.edu

Our lab is interested in understanding the signaling pathways that regulate mitochondrial function and turnover in cardiac myocytes. Defects in these pathways contribute to loss of cardiac myocytes and development of heart failure.  Cardiac myocytes are highly active cells that require large amounts of energy supplied by mitochondrial oxidative phosphorylation. Since mitochondria are critical to myocyte function, it is not surprising that there is a strong link between mitochondrial dysfunction and cardiovascular disease. Defective mitochondria can also activate of cell death pathways which can lead to loss of cardiac myocytes and reduced ability to sustain contractile function. This ultimately contributes to the development of heart failure. Therefore, the ability of the cell to overcome mitochondrial damage requires removal of the impaired mitochondria via autophagy.Autophagy is an evolutionarily conserved process involved in the degradation of long-lived proteins and organelles.

Project #1: The E3 ubiquitin ligase Parkin plays an important role in labeling dysfunctional mitochondria for degradation in cells. Parkin is normally localized in the cytosol but rapidly translocates to damaged mitochondria to promote their degradation by ubiquitinating proteins in the outer mitochondrial membrane. The ubiquitin serves as a signal for autophagic degradation. This project will explore the mechanisms underlying Parkin-mediated clearance of mitochondria in cells.

Project #2: MCL-1 is an anti-apoptotic Bcl-2 protein which is expressed at high levels in the heart compared to other anti-apoptotic Bcl-2 proteins. However, very little is known with respect to how MCL-1 regulates cell survival in cardiac myocytes. We have discovered that cardiac specific deletion of MCL-1 lead to mitochondrial dysfunction and rapid development of heart failure, suggesting that MCL-1 is critical for myocyte survival. We have found that one function of MCL-1 is to promote degradation of damaged mitochondria. In this project, the student will investigate the molecular mechanisms by which MCL-1 regulates mitochondrial clearance in cells.

 

Chitra Mandyam

Department of Anesthesiology

cmandyam@ucsd.edu

Our research is focused on understanding the mechanisms by which addiction to illicit drugs and alcohol affect brain stem cells and their function.
Our lab addresses this emerging neuroscience question by using high profile behavior models that mimic abuse and dependence to methamphetamine and alcohol. We use operant self-administration addiction models combined with biochemistry, histology, electrophysiology and learning and memory functions to determine the role of neural stem cells and glial progenitors in the adult mammalian brain in the pathophysiology of addiction.
We have 3 types of projects: We have recently discovered that newly born neurons in the hippocampus via a process called neurogenesis during abstinence from drug contribute to or enhance propensity for relapse. We are currently doing experiments using transgenic rats and genetic approaches to determine the neural circuitry underlying this maladaptation in the hippocampus.
We have also discovered that nonneuronal cells in the prefrontal cortex play a role in disturbing neuronal plasticity and promote relapse to alcohol seeking. We are currently doing experiments using transgenic rats and pharmacological tools to determine the functional significance of oligodendroglial cells and endothelial cell adhesion molecules in the prefrontal cortex in relapse to alcohol seeking.
In collaboration with Dr. Brian Head and Dr. Hemal Patel in the department, we have recently discovered that the membrane/lipid raft protein Caveolin-1 in the dorsal striatum may play a role in reinforcing properties of the psychostimulant methamphetamine. Ongoing experiments will determine the functional significance of this protein in methamphetamine addiction and discover new avenues to treat addiction.
Students will be exposed to animal behavior, biochemical studies including Western blotting, histology including immunohistochemistry, stereology and electron microscopy and electrophysiological studies including slice physiology.

Must have a GPA of 3.5 or higher, must be motivated to do basic science research; must have an understanding of biochemistry and cell biology. Previous lab experience is not necessary but welcome.
Please Submit: Resume, Cover Letter, Unofficial Transcript

David K. Welsh

dkwelsh@ucsd.edu

Department of Psychiatry

Project related to circadian rhythms in brain cells, and relation to depression-like behavior in mice.

Some lab experience who has taken the basic undergrad Circadian Biology course

Joanne Chory

chory@salk.edu

Plant Biology Laboratory

SALK Institute

Project 1:  Heat stress and global warming of plants

Environmental stresses such as heat and drought have adverse effects on plant growth and crop yield. Heat stress is one of the major abiotic stresses to plants and it now occurs more frequently as a consequence of global warming. This project will use genetic screening and molecular biology methods to identify genes that are involved in chloroplast signaling-controlled plant heat stress response pathways. We have already isolated some mutants resistant to heat stress and next work will be mainly focused on assaying the phenotypes of the mutants, mapping corresponding mutated genes from the mutants using high-throughput sequencing technology and validating gene functions. The major lab techniques will include: plant management, sample collection, plant crossbreeding, genotyping, seeds collection as well as molecular biology experiments like gene cloning, PCR, next-generation sequencing and data analysis. More detailed experiments will be set up based on the research progress of the project. You will work with and be supervised by a postdoc research associate in the lab.

Project 2:  Protein kinase function in plant temperature responses

This project will examine the role of an uncharacterized protein kinase in light and temperature responses in the model plant, Arabidopsis thaliana. This kinase is related to well-characterized genes in animals. As this gene has not previously been studied in plants, the initial steps of the project will be constructing and confirming molecular and genetic tools. The student will generate transgenic plants expressing mutant versions of the kinase, with the possibility of generating novel alleles using the CRISPR-Cas9 system. These and other tools will be used to characterize physiological responses to environmental light and temperature conditions, and examine possible genetic or biochemical interactions with known pathways. This work will be performed under the mentoring of a postdoctoral fellow in the Chory laboratory.

Paula Desplats

pdesplat@ucsd.edu

Department of Neuroscience

1. Dynamic DNA methylation and circadian alterations in Alzheimer's disease.

Disruptions in circadian regulation are a prominent clinical feature and a major factor of hospitalization and morbidity in Alzheimer's disease (AD). We recently uncovered alterations in the expression of the circadian clock gene BMAL1 in patient-derived fibroblasts and postmortem brain samples from early and late AD cases, associated with aberrant patterns of DNA methylation ( Cronin et al 2016, Alz & Dementia). We are currently investigating the mechanisms that regulate cyclic methylation and how these become altered in AD.

Exploring the impact of circadian alterations in neuronal physiology we also identified Insulin Degrading enzyme (IDE), involved in both, insulin signalling and amyloid-b clearance, as a circadian output directly regulated by BMAL1. We are investigating IDE regulation and its role in brain insulin resistance in AD.

2. Role of DNA methylation on modulating inflammation in Alzheimer's disease.

Neuroinflammation correlates with onset of AD and cognitive decline, and it is implicated in the pathological cascade leading to amyloid plaques. The role of epigenetic mechanisms on modulating inflammation is yet poorly understood. My current research seeks to identify alterations in DNA methylation on inflammation-related genes that may contribute to AD.

We recently completed genome-wide methylation analysis on postmortem frontal-cortex samples from subjects with AD and mild cognitive impairment (MCI) and identified multiple differentially methylated genes associated with immune response and inflammation. Using human primary microglial cells as in vitro model we are currently investigating imbalances in methylation enzymes and applying CRISPR/Cas9 technology to attempt epigenetic editing of inflammatory targets.

3. Alterations in autophagy-regulating miRNAs and oligodendroglial accumulation of a-synuclein in Multiple Systems Atrophy (MSA).

After identifying miR101 as an autophagy-regulating microRNA altered in MSA brains we are now interested in understating how changes in miRNAs that regulate vesicle sorting and autophagy contribute to pathological accumulation of a-synuclein in oligodendrocytes in MSA. Pairing my expertise in proteostasis and epigenetics with Regulus Therapeutics, an industry leader in miRNA therapy, we are evaluating the potential of modulating autophagy-inhibiting miRNAs to reduce a-synuclein accumulation as a therapeutic approach for this devastating disease.

GPA 3.5 or higher

Hands-on experience (by working on previous lab) in at least one of the techniques below:

  1. Cell culture
  2. Western blot and protein extraction
  3. RNA isolation and qPCR
  4. DNA isolation / cloning / minipreps
  5. Immunohistochemistry / microscopy
  6. 15 hours/week minimum dedication

Alessandra Franco

alfranco@ucsd.edu

Pediatrics

"Human T cell recognition with emphasis in immune regulation, fine specificity and function of regulatory T cells. Disease models: Kawasaki disease (pediatric Immunology), Rheumatoid Arthritis (autoimmunity)"

Ulupi Jhala

ujhala@ucsd.edu

Pediatrics

Project 1) Examination of Age dependent change in chromatin in pancreatic beta cell-specific knock out of a key transcription factor.

The project involves standardization of ChIP  (Chromatin IP) assays using cell lines and primary islets, followed by ChIP sequencing (using the Genome Sequencing facilities at UCSD) of previously isolated primary tissue from the KO mice.  The student would also help computational analysis of the data.  You will receive guidance and input with all aspects of the project.

Lab course in Molecular biology.

Coursework in basic biochemistry and molecular biology.

Julian Schroeder

jischroeder@ucsd.edu

Cell and Developmental Biology

Julian Schroeder’s laboratory has availability for BS/MS students. Research in the laboratory focuses on how plants can withstand environmental stresses, in particular drought and how plants respond to the continuing increase in the atmospheric CO 2 concentration. Both of these research projects have profound implications for developing more drought resistant crops. In addition, we pursue research on the molecular mechanisms by which plants accumulate toxic heavy metals towards bioremediation and avoiding heavy metal accumulation in edible tissues of crop plants.

BS/MS students are trained in laboratory research methods and pursue their own research experiments. 

 

William Joiner

wjoiner@ucsd.edu

Pharmacology

There are two major directions to my lab’s research. (1) We study sleep and its relation to memory formation.  This work involves use of molecular biology, biochemistry, immunohistochemistry and various behavioral assays to identify neural circuits and molecular mechanisms that regulate sleep/memory. We use fruit flies for these studies. Related work by other labs was awarded the Nobel Prize in 2017. (2) We also study the functions of proteins in the mammalian brain from which snake venom toxins evolved. Our data indicate that these important brain proteins regulate the subcellular trafficking, activity and pharmacology of receptors implicated in nicotine addiction, schizophrenia and Alzheimer’s disease.

  Potential projects:

1) Determine if sleep rewires the brain. This work will involve genetics, molecular biology (including CRISPR), microdissections and confocal microscopy.

2) Define neural circuits that regulate sleep and memory. This work will involve genetics, behavioral assays, microdissections and confocal microscopy.

3) Determine the functions of newly identified sleep-regulating genes. This work will involve genetics, behavioral assays, molecular biology (including CRISPR), microdissections and confocal microscopy.

4) Determine the mechanisms of action of newly discovered regulators of brain neurotransmitter receptors. This work will involve molecular biology, cell culture, biochemistry, and fluorescent pharmacological assays of brain receptor activity.

Soumita Das

sodas@ucsd.edu

Pradipta Ghosh

prghosh@ucsd.edu

Departments of Medicine and Cell and Molecular Medicine

General Background/Our accomplishments:

Our lab strives to study the cell biology of signal transduction, with a focus on heterotrimeric G-proteins (trimeric-GTPases). These classes of G proteins have been found on a variety of intracellular membranes since the early 1990’s; what they do there remained a mystery. We have systematically pursued in-depth the biological implications of this intracellular trimeric-GTPase system; it is modulated by a novel family of guanine-nucleotide exchange modulators (GEMs) and is fundamentally distinct from the conventional trimeric-GTPase signaling from the cell surface by G protein-coupled receptors (GPCRs).

We were one of the original discoverers of this signaling system beginning with the discovery of GIV-GEM, and subsequently extending to 3 other members (NUCB1/2 and Daple-GEMs). We showed that GEMs serve as vital platforms for intracellular communication networks; they coordinate cellular responses and organellar function in cells responding to environmental signals initiated by diverse classes of receptors, thereby allowing non-GPCRs to engage with and modulate trimeric-GTPases. Using the powerful synergy of cell, molecular and structural biology, molecular imaging, systems biology and bioinformatics, we showed the crucial importance of the GEM system in coordinating diverse cellular processes and revealed the mechanistic basis of their GEM action. As a physician-scientist, my group relentlessly pursued why/how aberrations in the GEM system spur pathogenic conditions such as cancer progression, fibrosis and insulin resistance, and provided the impetus to develop drugs targeting GEMs in these and other disease states.

Although modulation of trimeric-GTPases by GPCRs remains a core target of modern medicine, our discoveries have revealed that trimeric-GTPase signaling via GEMs is just as important, if not more, for coordinating cellular responses in physiology and for diagnosing and alleviating human suffering.

Specific projects/areas of current interests available for postdoc fellows:

  • Tightening the Gut Barrier to combat infectious, chronic diseases: The compromised intestinal barrier is associated with chronic diseases such as obesity, diabetes, inflammatory bowel diseases, metabolic endotoxemia and so far there is no clinical treatment is viable for the treatment of barrier loss. After encountering the pathogenic attacks or with the exposure of microbial products or toxic components from the environment, the epithelial tight junctions collapse and promote the diseases. Here we propose to understand the molecular mechanism of host pathway that can protect the integrity of the epithelial barrier that can be targeted to prevent the progression of chronic diseases. The project will use the cutting-edge stem cell based technology to isolate enteroids from murine and human (healthy and inflammatory bowel diseases) intestine, infection with pathogenic and non-pathogenic gut bacteria, testing of several signalling pathways and functional assays to understand the mechanism of gut barrier loss.
  • Decision points in macrophage polarization and the innate immune response: Implications in colitis . Inflammatory bowel diseases (IBD; Crohn’s disease and ulcerative colitis) are devastating conditions that affect 1 million people in the US and for which no lasting therapy currently exists. Several treatments for IBD aim to reduce inflammation by targeting inflammatory effectors, but none target dysfunctional macrophages. Because the molecular mechanisms that govern inflammatory responses in macrophages are not fully elucidated or exploited as therapeutic targets, there is a need that is both urgent and unmet. Using a combination of biochemical, cell biological, RNA-sequencing, and primary cell culture approaches we have identified GIV, a non-receptor GEF essential for the TLR4-G-protein signaling axis, as a key determinant of macrophage polarization and inflammatory cytokine production. As cell biologists, we intend to chart out the various steps during pathogen engulfment and clearance (via phagolysosomal maturation) that are regulated by GEMs, and interrogate mechanisms by which pathogens hijack the pathway to escape such clearance. Preliminary results have established the GIV→Gai signaling axis as a central signaling pathway in macrophage inflammatory responses and for bacterial uptake and clearance, and provide proof-of-principle for therapeutic targeting of GIV-GEF in IBD.
  • G proteins in injury, inflammation and repair : This project entails understanding the role of GIV in serving as a central hub that simultaneously amplifies pro-fibrogenic and down-regulates anti-fibrogenic signals in specialized myofibroblasts (hepatic stellate cells) during liver fibrosis and cirrhosis. Specifically, in this project we seek to elucidate the role of G proteins in modulating signals downstream of receptors that are known to enhance fibrogenic programs (TGFbeta, PDGF, TLR4, IL17) and how these receptors use GIV and/or Daple GEMs to alter downstream signaling cascades. We use human specimens for pathologic studies and additionally work with zebrafish as a model of chronic liver disease, simulating the pro-fibrogenic effect of alcohol abuse. Additionally, we are generating GIV knockout hepatic stellate cells using Crispr/Cas9 to further delineate its effect in various receptor downstreampathways.

Regulation of planar cell polarity, and implications during development and in cancer : This project involves understanding how the signaling scaffold, Daple (the second member of the GEM family), has two opposing functions during colorectal cancer progression; it serves as a tumor suppressor during the initial stages, but switches to an oncogene during late stage cancer progression. Using both zebrafish and cellular models of colorectal cancer, we seek to address if differential localization and/or post-translational modification of Daple controls this switch. Furthermore, proteomic studies on Daple-interacting proteins, identified by proximity labeling, have revealed novel binding partners, which provide valuable and exciting clues to the role of Daple in cells. Several of these findings promise a tectonic shift amongst paradigms in signal tra

  • Structural basis for the action of GEMs, and their potential as druggable targets : Signals initiated by multiple Receptor Tyrosine Kinases (RTKs) converge on the protein Gα- Interacting Vesicle associated protein (GIV) to trigger non-canonical transactivation of the trimeric G protein Gαi, the consequences of which have been demonstrated to be far-reaching and important for a diverse set of biological processes in both health and disease. Despite insights gained, the structural basis for this unusual G protein activation by GIV has remained a mystery and as such, drug development to target this pathway for therapeutic intervention in a wide variety of diseases has thus far not been possible. Ongoing work in the lab utilizes x-ray crystallography, enzymology, differential scanning fluorimetry, and various biochemical approaches to investigate the structural basis for GIV-dependent G protein activation at the atomic level. These structural insights are now allowing us, in collaboration with the Sanford Burnham Prebys drug discovery team, to conduct targeted high-throughput screening for the development of small molecule drugs to disrupt this RTK-GIV-Gαi pathway in human disease.
  • Structure-based identification of novel GEMs in the human genome : Using the solved structure (above), we have identified a few other putative GEMs in the human genome—these are proteins engaged in diverse cellular processes and signaling within distinct pathways. Some already have disease associations [via GWAS studies], whereas others have been found to be critical signal transducers whose aberrations are associated with multiple diseases.
  • Other projects studying the role of GEMs and the G proteins in cellular processes : Our lab continues to explore the roles of GEMs at various places within cells, and the impact of such localization and their G protein regulatory effect on various cellular processes at those locations. Some of the ongoing projects include: a) polarized exocytosis; b) DNA damage repair; c) mitochondrial dynamics; d) cell-cell junctions and epithelial barrier function.

Preference will be given to candidates with good grades and prior laboratory experience.

Alon Goren

agoren@ucsd.edu

Department of Medicine

Projects Available

General theme

Our interdisciplinary research focuses on epigenomic mechanisms and their dynamics. To this end, we merge basic biology, technological innovations and computational analyses. We are mainly interested in understanding the role of chromatin regulation in development and disease states, such as cancer and autism. Additional details can be found at the lab website: goren-lab.github.io

Project description

We have three projects that would fit well a BS/MS student:

  1. Dissecting the role of H3K27me3 in establishment and maintenance of pluripotency. Regulating gene activity in cells is mainly achieved by how DNA associated proteins are organized, collectively known as chromatin structure. The goal of this research project is to understand how the chromatin structure is used for cell differentiation. In particular, we study how pluripotency is established in vivo and maintained in vivo, focusing on the role of H3K27me3, a key repressive histone modification deposited by the polycomb group complex (PcG). For this, we leverage key differences distinguishing in vivo inner cell mass (ICM) and in vitro mouse embryonic stem cells (mESCs).
  2. Development of a novel method to chart genomic localization of protein complexes in vivo. Defining the genomic organization of DNA associated proteins is critical for deep understanding of the regulatory mechanisms governing cellular states. However, ChIP-seq, the primary methodology used for mapping DNA associated proteins has several major limitations. For instance, standard ChIP-seq is unable to profile more than one epitope at one time in one sample and the reliance on an inefficient immunoprecipitation step, resulting in signal reduction. A key challenge in chromatin biology is to study the organization of multiple DNA binding proteins simultaneously from a single sample and to identify instances where these proteins are bound to the same genomic molecule originating from a single cell. 

    The project is aimed at the development of a novel methodology designed to overcome ChIP-seq limitations and apply this innovative method to study co-association of chromatin regulators, employing the embryonic stem cells as a model system. The new method developed in this project will provide a means to obtain an unprecedented view of the different combinatorial signatures of chromatin regulators, the dynamics of their formation during differentiation and how these signatures may go awry in disease.

  3. Interrogating regulatory consequences of genetic variation in DNA associated proteins (jointly with the Gymrek Lab https://gymreklab.github.io/): Mutations in proteins inducing widespread transcriptomic changes are widely implicated in human disease. Intriguingly, different mutations in the same gene can result in multiple distinct phenotypes. This project develops a high-throughput genome editing technique to simultaneously measure the regulatory impact of hundreds of protein-altering mutations in a particular DNA-associated protein using single-cell RNA sequencing, with the ultimate goal of interpreting genetic changes leading to human disease.

We are looking for a highly motivated student, with interest in molecular and computational biology and epigenomics that wishes to work in a dynamic, multidisciplinary research environment. We will only consider students that have maintained a minimum of 3.7 GPA and are highly committed, hardworking and enthusiastic. Students should be able to work for at least 20 hours per week over school year and full time during the summer. The required minimal commitment is one year.

Eric Halgren

ehalgren@ucsd.edu

Radiology

The general state of the human organism is modulated by the autonomic system comprised of two balancing influences: sympathetic and parasympathetic. This study proposes to stimulate locations on the external ear which have sympathetic and/or parasympathetic sensory fibers, at a frequency which produces no conscious sensation, but which evokes a mild autonomic response, measured as pupillary dilation, skin conductance, and heart rate. The sympathetic and parasympathetic systems are linked in the brainstem with the ascending modulatory projections which set general cortical activity levels and operating modes. The purpose of this study is to determine if weak stimulation of the external ear also modulates cortical activity in humans, and if so characterize that modulation.

  1. In healthy subjects, use autonomic measures and EEG to estimate the response to stimulation of the external ear in locations innervated by the sympathetic and/or parasympathetic system.
  2. Analyze autonomic measures (pupillary dilation, skin conductance, and heart rate variability) to separately characterize the response of the sympathetic and parasympathetic systems.
  3. Analyze event-related and spontaneous EEG measures in the time and frequency domains to estimate cortical functional state, and relate it to autonomic effects.
  4. In patients with intracranial electrodes for localization of spontaneous seizure onset, also record neural activity in cortical and subcortical locations to estimate the event-related neural effects of the stimulation.
  5. Analyze autonomic measures to confirm that the autonomic effects are occurring and determine their time course and magnitude.
  6. Analyze event-related and spontaneous local field potentials and high gamma power in the time and frequency domains to estimate cortical functional state, and relate it to autonomic effects.

We hypothesize that external ear stimulation will produce mild event-related autonomic and cortical modulation, without conscious perceptual effects, and that these effects will be primarily sympathetic or parasympathetic according to the location where the stimulation is applied. The ultimate significance of this knowledge will be to permit the development of new non-invasive methods to modulate brain activity, and thus potentially treat a variety of illnesses, as diverse as insomnia, Alzheimer’s Disease (where the lack of slow waves are hypothesized to have a causal role), and asthma (which is modulated by the parasympathetic system).

In collaboration with a Neurosciences MD/PhD student, and under the supervision of the Principal Investigator (Eric Halgren, Professor of Neuroscience and Radiology, UCSD), the student will have co-responsibility for the above studies, including assisting in writing up and publishing the results. IRB approval and funding have been obtained and the study is ready to start. Familiarity with Matlab and Linux would be important, familiarity with electrophysiological recording methods useful but not essential.

Milton Saier

msaier@ucsd.edu

Molecular Biology

Projects include:

1) Bioinformatics: Determining family relationships (homology, topology, phylogenetic tree construction, diversity of distribution in the world of Biology, etc.)

2) Biochemistry/Bacterial Physiology: Determining the function of a particular gene product 

3) Molecular Genetics: Determining mutation rates under varied conditions and in different genetic backgrounds

All students start in the dry lab for the first quarter. Interested students must have at least a 3.2 GPA and commit to at least 12 hours per week.