2007 MCRTP Scholars

Andrew Bremer, MD, PhD, Department of Pediatrics

Mentor: Dennis Styne, MD

Title of Research:  PC-1 as a Biomarker of Insulin Resistance

Insulin resistance plays a major role in the pathophysiology of type 2 diabetes (T2D) and the insulin resistance syndrome, both important causes of morbidity and mortality worldwide. Furthermore, insulin resistance is present in ~25% of the non-obese/non-diabetic population, causing compensatory hyperinsulinemia and increasing the risk for T2D, cardiovascular disease, polycystic ovary syndrome, and certain forms of cancer. Membrane glycoprotein PC-1 (ENPP1) is an inhibitor of the insulin receptor, and we hypothesize that it may be a major target molecule in the pathogenesis of insulin resistance. Human genetic studies, in vitro cell studies, and in vivo animal studies have all shown correlations between insulin resistance and increased PC-1 expression and/or activity. The ability to study PC-1 and its association with insulin resistance in the general population is, however, hampered by the current need for a tissue biopsy to analyze the protein, which is impractical to perform on large numbers of individuals in modern clinical practice. If a rapid blood-based test could be developed to non-invasively evaluate an individual's PC-1 genotype and level of expression and activity, then analyzing PC-1 status in the general population would be possible. This project aims to validate the use of PC-1 from blood elements as a biomarker of insulin resistance, thus permitting the early identification and treatment of individuals at risk for PC-1 mediated insulin resistance-related diseases.

Benjamin Davis, PhD, Center for Health and the Environment

Mentor: Kent Pinkerton, PhD

Title of Research:  Novel Treatments for Inflammatory Lung Disease with Inhibitors of Soluble Epoxide Hydrolase

Lung inflammatory diseases are a major cause of mortality and illness worldwide. Unfortunately, there are few effective therapies for these diseases. Work from our lab has demonstrated that the enzyme soluble epoxide hydrolase (sEH) is necessary for a normal inflammatory response and that inhibitors of this enzyme represent a potential novel class of anti-inflammatory drugs. We have recently demonstrated that an inhibitor of sEH reduces tobacco smoke-induced lung inflammation and have developed a new generation of orally available sEH inhibitors that will easily translate to the clinical setting. Despite their promise, the mechanism of action of these compounds as anti-inflammatory agents is poorly understood. We hypothesize that an increase in epoxyeicosatrienoic acids (EETs) is the underlying cause of the anti-inflammatory effects of sEH inhibitors and that EETs mediate this effect by acting on vascular endothelium to block the recruitment of inflammatory cells to the site of inflammation. We will test this hypothesis using an in vivo model of tobacco smoke-induced lung inflammation and an in vitro model of neutrophil adhesion. Lastly, we will determine if the changes in the plasma concentration of sEH substrates and metabolites we observe in an animal tobacco smoke model are conserved in human smokers.

Sean Deane, MD, Rheumatology/Allergy and Clinical Immunology

Mentor:  M. Eric Gershwin, MD

Title of Research:  Identification of Novel Cell Surface Ligands and Small Molecules that Interact with Intracellular Signaling Proteins in Mammary Stem Cells

Adult stem cells are defined by their capacity for self-renewal and differentiation into cell lineages present in a specific tissue. Our overall project goal is to assess the role of stem cells in breast cancer. For this, we initially propose to use a mouse transgenic model in which the tumors produced closely resemble human tumors. We would like to identify cell surface ligands that bind specifically to breast cancer stem cells. It is our intent to initially determine the cell surface characteristics of mammary stem cells, then peptidomimetic and small molecules that interact with intracellular signaling proteins. This may involve assessing pathways that can be altered or pathways that, if up- or down-regulated, may lead to apoptosis or loss of cell viability. These studies could lead to identification of important markers of stem cells that could be critical to the identification of a normal vs. malignant stem cell. Through combinatorial chemistry, ligand or inhibitors for a variety of targets can be identified and used to study the biological function of the target proteins, potentially identifying novel therapeutic options. With a view towards that eventual target, our immediate objective is to determine the cell surface profiles of mammary stem cells.

Anuurad Erdembileg, MD, PhD, Division of Endocriniology/Clinical Nutrition

Mentor:  Lars Berglund, MD, PhD

Title of Research:  The Constellation of Metabolic Syndrome as a Modulator of Cardiovascular Disease Across Ethnicity

A cluster of metabolic abnormalities, defined as the metabolic syndrome, including hypertriglyceridemia, low HDL-cholesterol, hypertension, abdominal obesity, and increased fasting glucose levels has been associated with subsequent development of diabetes mellitus and cardiovascular disease. The pathogenesis of the metabolic syndrome is poorly understood, but the syndrome has likely multiple origins including genetic and environmental factors such as obesity, diet, and sedentary lifestyle. There are, however, substantial differences among these metabolic abnormalities across ethnic groups and gender. Further, the metabolic syndrome is a pro-inflammatory condition. While this may be due to various contributing mechanisms, it is notable that HDL is associated with an anti-inflammatory effect. Finally, genetic variants such as apoE polymorphism play a key role in lipid metabolism. We and others have demonstrated a protective effect of the apoE2 genotype. We hypothesize that this protective effect may be mediated through modulation of components of the metabolic syndrome and through reduction of inflammatory biomarkers. Specifically, we will analyze the constellation of metabolic syndrome components in subjects with different apoE genotypes as well as the association of apoE genetic variation with inflammatory biomarkers.

Nasim Fazel, MD, Department of Dermatology

Mentor:  R. Rivkah Isseroff, MD

Title of Research: Salivary Catecholamines in Recurrent Aphthous Stomatitis

Recurrent aphthous stomatitis (RAS) is the most common oral ulcerative condition in the United States, with an estimated mean prevalence of 20%. Occurring generally between the ages of 10 and 19, this condition usually heals itself without scarring in 1 to 2 weeks. However, moderate and severe cases do exist where the patients suffer from significant pain and discomfort that can deeply affect their oral intake and quality of life. Considerable research has been devoted to identifying potential causes of RAS; however, the principal etiology of this condition remains obscure. Here we propose a novel approach to the disease: that it is exacerbated by stress-induced intraoral increases in salivary catecholamines, and that it can be treated by blockade of the beta adrenergic receptors that mediate the catecholamine response. This proposal encompasses two phases, an initial wet laboratory phase that will be in collaboration with my mentor, followed by a clinical trial in which I will be the principal investigator. I will initiate the clinical trial concurrent with the MCRTP program and will leverage the resources available to me in the program. The second phase will allow me to develop into an independent clinical research investigator.

Karl Jandrey, DVM, DACVECC, School of Veterinary Medicine

Mentor:  Fern Tablin, VMD, PhD

Title of Research:  Platelet Upregulation: Alterations in Receptor Activation and Agonist Sensitivity Associated with Feline Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most common type of heart disease in cats. Aortic thromboembolism secondary to HCM is a relatively common veterinary emergency that has minimally effective therapy and is frequently fatal. Endothelial damage, alterations in blood flow, and release of ADP from aggregated red blood cells all lead to platelet upregulation and hyperaggregability that promote thrombi formation. Our hypothesis is that platelet up-regulation is the key element leading to thromboembolism in HCM. There is currently no simple analytical tool available for the evaluation of the hyper-coaguable state in cats. Current platelet function studies in our laboratory comparing normal cats to those with hypertrophic cardiomyopathy have found flow cytometry to be a much more sensitive assay than a currently existing method. Our proposed studies will correlate the flow cytometry derived data to the degree of severity of HCM cats as defined by echocardiography.

Brian Lim, MD, Department of Gastroenterology

Mentor:  Joseph Leung, MD

Endoscopic retrograde cholangiopancreatography (ERCP) is a technically demanding procedure that can cause substantial complications. For this reason, there has been an increased interest in establishing the minimum threshold of procedures needed for an assessment of competency. I will be working with Dr. Leung and other mentors in further advancing the training and assessment of trainees using these mechanical simulators and its clinical applicability. This will be accomplished through a two-fold approach involving papillotomies, which carry a high risk of bleeding, pancreatitis, and perforation. First, I will conduct a prospective study comparing the rate of complications (i.e., bleeding and post-ERCP pancreatitis) between papillotomies done in the correct axis and those outside of this axis. The patients who had papillotomies will be prospectively followed for development of complications. Second, we will conduct a study to show that papillotomy scores improve after repeated training of the fellows using the mechanical simulator. I will specifically look at the trainees' clinical improvement after having gone through the training sessions. The hypothesis here is that the trainees who complete the simulator training will show significantly greater improvement of papillotomy techniques than those in the control arm.

Steve Martinez, MD, Department of Surgery

Mentor:  Richard J. Bold, MD

Our approach is to combine novel imaging techniques with blood molecular/genetic markers to fundamentally alter the way patients with locally advanced breast cancer are managed before, during, and after pre-operative chemotherapy. We anticipate that this combined approach will improve patient selection, more accurately predict response to chemotherapy, potentially alter the extent of surgery, and provide important information regarding the likelihood of disease recurrence. We will use repeated breast positron emission tomography/computed tomography (PET/CT) to assess serial tumor response. In addition, a blood-based assay (our collaborators at John Wayne Cancer Institute have developed novel assays to detect serum circulating tumor-related DNA) reflective of "real time" tumor status will be used in conjunction with anatomic and functional imaging to assess response to therapy while treatment is ongoing and compared to findings on breast PET/CT, as well as the final assessment of clinical and histopathologic response.

Uma Srivatsa, MD, Department of Internal Medicine/Cardiovascular

Mentor:  Nipavan Chiamvimonvat, MD

Title of Research:  Heat Shock Protein Production in Cardiac Muscle is Induced by Exercise Training and Potentially Improves Responsiveness to Cardiac Resynchronization Therapy and Reduces Atrial Arrhythmias in Patients Receiving Defibrillators

In patients with congestive heart failure from left ventricular (LV) systolic dysfunction, who undergo device implantation, exercise training induced heat shock proteins (Hsp's) are responsible for improvement in exercise capacity, and can potentially play a role in reduction in incidence of arrhythmias. There may be variations in Hsp response depending on the severity of heart failure and the extent of exercise capacity. This project involves an open label randomized prospective clinical trial to assess the correlation between higher Hsp levels and better clinical outcomes as assessed by VO2 max, improvement in a 6-minute salk test, and echocardiographic parameters.

Beverly Sturges, DVM, Veterinary Medicine: Department of Surgical and Radiological Sciences

Mentor:  Jan Ilkiw, BVSc, PhD, DECVA

Title of Research:  Preemptive Gabapentin Administration Reduces Pain and Opiod Requirements Following Spinal Surgery in Dogs

Gabapentin is an anticonvulsant drug that has been shown to produce analgesia in several models of chronic pain. Three recent human clinical studies showed that the preemptive administration of gabapentin undergoing spinal surgery improved pain relief compared to the administration of opiods alone, and allowed a reduction in opioid consumption associated with a decrease in adverse effects. In this study, we propose to determine whether preemptive gabapentin administration improves post-operative analgesia after thoracolubar laminectomy and discectomy in a canine model.

Ruth Vinall, PhD, Department of Urology

Mentor:  Ralph de Vere White, MD

Title of Research:  Dual AKT Inhibition with Perifonsine and GCP Enhances Apoptosis in Prostate Cancer: Investigation of Mechanism of Action and Clinical Validation

A clinical trial of GCP/perifosine in prostate cancer (CaP) patients is presently in development at the UC Davis Cancer Center. Understanding the mechanism(s) by which apoptosis is induced in CaP is key for the development of successful and long lasting treatments for this disease, and for the selection of patient populations who may benefit the most from these treatments. Our hypothesis is that GCP and perifosine can increase apoptosis of prostate cancer cells by targeting two different components of the Akt signaling pathway and/or by mimicry of androgen ablation combined with blocking the Akt cell survival pathway, and that p53 plays an important role in facilitation this GCP/perifosine-induced apoptosis.

Amir Zeki, MD, Division of Pulmonary & Critical Care Medicine

Mentor:  Nicholas Kenyon, MD

Title of Research:  Asthma Exacerbations and Statins

I am interested in the potential effects of statins in ameliorating airway inflammation, particularly in asthma. There are both animal and human data implication the role of the statin drugs in modifying and modulating a wide array of inflammatory responses, including respiratory disease. My research will address the hypothesis that severe asthmatics on a statin drug have fewer exacerbations than those not treated with statins. This study will involve patients at the UC Davis Asthma Network that have severe asthma, and the degree of exacerbations will be determined through retrospective chart review.

2006 MCRTP Scholars

Stephen Franklin, MD, Department of Radiology/Oncology

Mentor:  James Boggan, MD

Title of Research:  Daily Set-Up for Head and Neck Cancer IMRT: A Comparison of Immobilization Systems

Jay Han, MD, Department of Physical Medicine and Rehabilitation

Mentor:  Craig M. McDonald, MD

Title of Research:  MRI Evaluation and Characterization of Muscle in Duchenne Muscular Dystrophy

Kim Janatpour, MD, Department of Pathology and Laboratory Medicine

Mentor:  Ted Wun, MD

Title of Research:  Clinical Proteomics of Heparin Induced Thrombocytopenia (HIT)

Valentini Medici, MD, Department of Internal Medicine

Mentors:  Lorenzo Rossaro, MD, Charles Halsted, MD, and Natalie Torok, MD

Title of Research:  Liver Disease: Effect of SAM on Outcome of Alcoholic Steatohepatitis (ASH)

Mark Underwood, MD, Department of Pediatrics

Mentor:  Charles Bevins, MD

Title of Research:  Pathophysiology, Treatment and Prevention of Necrotizing Enterocolitis

Allison Zwingenberger, DVM, School of Veterinary Medicine, Surgical and Radiological Services

Mentor:  Erik Wisner, DVM

Title of Research:  Targeted Imaging of Spontaneous Canine Lymphoma with 2A-PMP-99Tc-PEG

Andrew Bremer, MD, PhD, Department of Pediatrics
Mentor: Dennis Styne, MD

Title of Research:  PC-1 as a Biomarker of Insulin Resistance

Insulin resistance plays a major role in the pathophysiology of type 2 diabetes (T2D) and the insulin resistance syndrome, both important causes of morbidity and mortality worldwide. Furthermore, insulin resistance is present in ~25% of the non-obese/non-diabetic population, causing compensatory hyperinsulinemia and increasing the risk for T2D, cardiovascular disease, polycystic ovary syndrome, and certain forms of cancer. Membrane glycoprotein PC-1 (ENPP1) is an inhibitor of the insulin receptor, and we hypothesize that it may be a major target molecule in the pathogenesis of insulin resistance. Human genetic studies, in vitro cell studies, and in vivo animal studies have all shown correlations between insulin resistance and increased PC-1 expression and/or activity. The ability to study PC-1 and its association with insulin resistance in the general population is, however, hampered by the current need for a tissue biopsy to analyze the protein, which is impractical to perform on large numbers of individuals in modern clinical practice. If a rapid blood-based test could be developed to non-invasively evaluate an individual's PC-1 genotype and level of expression and activity, then analyzing PC-1 status in the general population would be possible. This project aims to validate the use of PC-1 from blood elements as a biomarker of insulin resistance, thus permitting the early identification and treatment of individuals at risk for PC-1 mediated insulin resistance-related diseases.

Benjamin Davis, PhD, Center for Health and the Environment
Mentor: Kent Pinkerton, PhD

Title of Research:  Novel Treatments for Inflammatory Lung Disease with Inhibitors of Soluble Epoxide Hydrolase

Lung inflammatory diseases are a major cause of mortality and illness worldwide. Unfortunately, there are few effective therapies for these diseases. Work from our lab has demonstrated that the enzyme soluble epoxide hydrolase (sEH) is necessary for a normal inflammatory response and that inhibitors of this enzyme represent a potential novel class of anti-inflammatory drugs. We have recently demonstrated that an inhibitor of sEH reduces tobacco smoke-induced lung inflammation and have developed a new generation of orally available sEH inhibitors that will easily translate to the clinical setting. Despite their promise, the mechanism of action of these compounds as anti-inflammatory agents is poorly understood. We hypothesize that an increase in epoxyeicosatrienoic acids (EETs) is the underlying cause of the anti-inflammatory effects of sEH inhibitors and that EETs mediate this effect by acting on vascular endothelium to block the recruitment of inflammatory cells to the site of inflammation. We will test this hypothesis using an in vivo model of tobacco smoke-induced lung inflammation and an in vitro model of neutrophil adhesion. Lastly, we will determine if the changes in the plasma concentration of sEH substrates and metabolites we observe in an animal tobacco smoke model are conserved in human smokers.

Sean Deane, MD, Rheumatology/Allergy and Clinical Immunology
Mentor:  M. Eric Gershwin, MD

Title of Research:  Identification of Novel Cell Surface Ligands and Small Molecules that Interact with Intracellular Signaling Proteins in Mammary Stem Cells

Adult stem cells are defined by their capacity for self-renewal and differentiation into cell lineages present in a specific tissue. Our overall project goal is to assess the role of stem cells in breast cancer. For this, we initially propose to use a mouse transgenic model in which the tumors produced closely resemble human tumors. We would like to identify cell surface ligands that bind specifically to breast cancer stem cells. It is our intent to initially determine the cell surface characteristics of mammary stem cells, then peptidomimetic and small molecules that interact with intracellular signaling proteins. This may involve assessing pathways that can be altered or pathways that, if up- or down-regulated, may lead to apoptosis or loss of cell viability. These studies could lead to identification of important markers of stem cells that could be critical to the identification of a normal vs. malignant stem cell. Through combinatorial chemistry, ligand or inhibitors for a variety of targets can be identified and used to study the biological function of the target proteins, potentially identifying novel therapeutic options. With a view towards that eventual target, our immediate objective is to determine the cell surface profiles of mammary stem cells.

Anuurad Erdembileg, MD, PhD, Division of Endocriniology/Clinical Nutrition
Mentor:  Lars Berglund, MD, PhD

Title of Research:  The Constellation of Metabolic Syndrome as a Modulator of Cardiovascular Disease Across Ethnicity

A cluster of metabolic abnormalities, defined as the metabolic syndrome, including hypertriglyceridemia, low HDL-cholesterol, hypertension, abdominal obesity, and increased fasting glucose levels has been associated with subsequent development of diabetes mellitus and cardiovascular disease. The pathogenesis of the metabolic syndrome is poorly understood, but the syndrome has likely multiple origins including genetic and environmental factors such as obesity, diet, and sedentary lifestyle. There are, however, substantial differences among these metabolic abnormalities across ethnic groups and gender. Further, the metabolic syndrome is a pro-inflammatory condition. While this may be due to various contributing mechanisms, it is notable that HDL is associated with an anti-inflammatory effect. Finally, genetic variants such as apoE polymorphism play a key role in lipid metabolism. We and others have demonstrated a protective effect of the apoE2 genotype. We hypothesize that this protective effect may be mediated through modulation of components of the metabolic syndrome and through reduction of inflammatory biomarkers. Specifically, we will analyze the constellation of metabolic syndrome components in subjects with different apoE genotypes as well as the association of apoE genetic variation with inflammatory biomarkers.

Nasim Fazel, MD, Department of Dermatology
Mentor:  R. Rivkah Isseroff, MD

Title of Research: Salivary Catecholamines in Recurrent Aphthous Stomatitis

Recurrent aphthous stomatitis (RAS) is the most common oral ulcerative condition in the United States, with an estimated mean prevalence of 20%. Occurring generally between the ages of 10 and 19, this condition usually heals itself without scarring in 1 to 2 weeks. However, moderate and severe cases do exist where the patients suffer from significant pain and discomfort that can deeply affect their oral intake and quality of life. Considerable research has been devoted to identifying potential causes of RAS; however, the principal etiology of this condition remains obscure. Here we propose a novel approach to the disease: that it is exacerbated by stress-induced intraoral increases in salivary catecholamines, and that it can be treated by blockade of the beta adrenergic receptors that mediate the catecholamine response. This proposal encompasses two phases, an initial wet laboratory phase that will be in collaboration with my mentor, followed by a clinical trial in which I will be the principal investigator. I will initiate the clinical trial concurrent with the MCRTP program and will leverage the resources available to me in the program. The second phase will allow me to develop into an independent clinical research investigator.

Karl Jandrey, DVM, DACVECC, School of Veterinary Medicine
Mentor:  Fern Tablin, VMD, PhD

Title of Research:  Platelet Upregulation: Alterations in Receptor Activation and Agonist Sensitivity Associated with Feline Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most common type of heart disease in cats. Aortic thromboembolism secondary to HCM is a relatively common veterinary emergency that has minimally effective therapy and is frequently fatal. Endothelial damage, alterations in blood flow, and release of ADP from aggregated red blood cells all lead to platelet upregulation and hyperaggregability that promote thrombi formation. Our hypothesis is that platelet up-regulation is the key element leading to thromboembolism in HCM. There is currently no simple analytical tool available for the evaluation of the hyper-coaguable state in cats. Current platelet function studies in our laboratory comparing normal cats to those with hypertrophic cardiomyopathy have found flow cytometry to be a much more sensitive assay than a currently existing method. Our proposed studies will correlate the flow cytometry derived data to the degree of severity of HCM cats as defined by echocardiography.

Brian Lim, MD, Department of Gastroenterology
Mentor:  Joseph Leung, MD

Endoscopic retrograde cholangiopancreatography (ERCP) is a technically demanding procedure that can cause substantial complications. For this reason, there has been an increased interest in establishing the minimum threshold of procedures needed for an assessment of competency. I will be working with Dr. Leung and other mentors in further advancing the training and assessment of trainees using these mechanical simulators and its clinical applicability. This will be accomplished through a two-fold approach involving papillotomies, which carry a high risk of bleeding, pancreatitis, and perforation. First, I will conduct a prospective study comparing the rate of complications (i.e., bleeding and post-ERCP pancreatitis) between papillotomies done in the correct axis and those outside of this axis. The patients who had papillotomies will be prospectively followed for development of complications. Second, we will conduct a study to show that papillotomy scores improve after repeated training of the fellows using the mechanical simulator. I will specifically look at the trainees' clinical improvement after having gone through the training sessions. The hypothesis here is that the trainees who complete the simulator training will show significantly greater improvement of papillotomy techniques than those in the control arm.

Steve Martinez, MD, Department of Surgery
Mentor:  Richard J. Bold, MD

Our approach is to combine novel imaging techniques with blood molecular/genetic markers to fundamentally alter the way patients with locally advanced breast cancer are managed before, during, and after pre-operative chemotherapy. We anticipate that this combined approach will improve patient selection, more accurately predict response to chemotherapy, potentially alter the extent of surgery, and provide important information regarding the likelihood of disease recurrence. We will use repeated breast positron emission tomography/computed tomography (PET/CT) to assess serial tumor response. In addition, a blood-based assay (our collaborators at John Wayne Cancer Institute have developed novel assays to detect serum circulating tumor-related DNA) reflective of "real time" tumor status will be used in conjunction with anatomic and functional imaging to assess response to therapy while treatment is ongoing and compared to findings on breast PET/CT, as well as the final assessment of clinical and histopathologic response.

Uma Srivatsa, MD, Department of Internal Medicine/Cardiovascular
Mentor:  Nipavan Chiamvimonvat, MD

Title of Research:  Heat Shock Protein Production in Cardiac Muscle is Induced by Exercise Training and Potentially Improves Responsiveness to Cardiac Resynchronization Therapy and Reduces Atrial Arrhythmias in Patients Receiving Defibrillators

In patients with congestive heart failure from left ventricular (LV) systolic dysfunction, who undergo device implantation, exercise training induced heat shock proteins (Hsp's) are responsible for improvement in exercise capacity, and can potentially play a role in reduction in incidence of arrhythmias. There may be variations in Hsp response depending on the severity of heart failure and the extent of exercise capacity. This project involves an open label randomized prospective clinical trial to assess the correlation between higher Hsp levels and better clinical outcomes as assessed by VO2 max, improvement in a 6-minute salk test, and echocardiographic parameters.

Beverly Sturges, DVM, Veterinary Medicine: Department of Surgical and Radiological Sciences
Mentor:  Jan Ilkiw, BVSc, PhD, DECVA

Title of Research:  Preemptive Gabapentin Administration Reduces Pain and Opiod Requirements Following Spinal Surgery in Dogs

Gabapentin is an anticonvulsant drug that has been shown to produce analgesia in several models of chronic pain. Three recent human clinical studies showed that the preemptive administration of gabapentin undergoing spinal surgery improved pain relief compared to the administration of opiods alone, and allowed a reduction in opioid consumption associated with a decrease in adverse effects. In this study, we propose to determine whether preemptive gabapentin administration improves post-operative analgesia after thoracolubar laminectomy and discectomy in a canine model.

Ruth Vinall, PhD, Department of Urology
Mentor:  Ralph de Vere White, MD

Title of Research:  Dual AKT Inhibition with Perifonsine and GCP Enhances Apoptosis in Prostate Cancer: Investigation of Mechanism of Action and Clinical Validation

A clinical trial of GCP/perifosine in prostate cancer (CaP) patients is presently in development at the UC Davis Cancer Center. Understanding the mechanism(s) by which apoptosis is induced in CaP is key for the development of successful and long lasting treatments for this disease, and for the selection of patient populations who may benefit the most from these treatments. Our hypothesis is that GCP and perifosine can increase apoptosis of prostate cancer cells by targeting two different components of the Akt signaling pathway and/or by mimicry of androgen ablation combined with blocking the Akt cell survival pathway, and that p53 plays an important role in facilitation this GCP/perifosine-induced apoptosis.

Amir Zeki, MD, Division of Pulmonary & Critical Care Medicine
Mentor:  Nicholas Kenyon, MD

Title of Research:  Asthma Exacerbations and Statins

I am interested in the potential effects of statins in ameliorating airway inflammation, particularly in asthma. There are both animal and human data implication the role of the statin drugs in modifying and modulating a wide array of inflammatory responses, including respiratory disease. My research will address the hypothesis that severe asthmatics on a statin drug have fewer exacerbations than those not treated with statins. This study will involve patients at the UC Davis Asthma Network that have severe asthma, and the degree of exacerbations will be determined through retrospective chart review.

Stephen Franklin, MD, Department of Radiology/Oncology
Mentor:  James Boggan, MD

Title of Research:  Daily Set-Up for Head and Neck Cancer IMRT: A Comparison of Immobilization Systems

Jay Han, MD, Department of Physical Medicine and Rehabilitation
Mentor:  Craig M. McDonald, MD
Title of Research:  MRI Evaluation and Characterization of Muscle in Duchenne Muscular Dystrophy

Kim Janatpour, MD, Department of Pathology and Laboratory Medicine
Mentor:  Ted Wun, MD
Title of Research:  Clinical Proteomics of Heparin Induced Thrombocytopenia (HIT)

Valentini Medici, MD, Department of Internal Medicine
Mentors:  Lorenzo Rossaro, MD, Charles Halsted, MD, and Natalie Torok, MD
Title of Research:  Liver Disease: Effect of SAM on Outcome of Alcoholic Steatohepatitis (ASH)

Mark Underwood, MD, Department of Pediatrics
Mentor:  Charles Bevins, MD
Title of Research:  Pathophysiology, Treatment and Prevention of Necrotizing Enterocolitis

Allison Zwingenberger, DVM, School of Veterinary Medicine, Surgical and Radiological Services
Mentor:  Erik Wisner, DVM
Title of Research:  Targeted Imaging of Spontaneous Canine Lymphoma with 2A-PMP-99Tc-PEG