Congratulations Dr. Carroll Cross, recipient of the Internal Medicine Career Achievement Award!
Dr. Cross literally founded our division of Pulmonary/Critical Care Medicine in 1968 when he served as our chief. He likes to describe how he was one of the first “ten or twenty” faculty, not of the division or department, but of the School of Medicine. Over time, he has built an international reputation in research and education and clinical care and he remains extraordinarily active in local and national societies, much to the amazement of the other pulmonary faculty. As he has done throughout his career, Dr. Cross continues to read the literature fully and furiously. Nobody has ever seen anyone consume and grasp as many research papers as Carroll. Each week, pulmonary faculty gets a series of papers and abstracts to review in their mailbox. These papers are always in the investigators’ field and are usually seen first by Carroll. It is his way of taking care of the junior and mid-career faculty. It is truly awe-inspiring to witness this capacity to read and share the literature after forty plus years as a faculty member. How he maintains this practice certainly deserves further explanation if he wins this award!
Dr. Cross’ career long expertise has been in the fields of cystic fibrosis (CF), alpha-1 antitrypsin (A1AT) deficiency, and the generation and function of reactive oxygen species in the lung. He remains the director of the A1AT program and co-director of the CF program in our division. I have no idea what the exact publication count is for Dr. Cross but it is approaching 300 publications. A review of PubMed for his earliest manuscripts revealed three publications each in Circ Res and Am J Physiol in 1960! Many of his publications are cited over 50 times. In the past 20 years, I would highlight his papers in JBC, AJRCCM, Free Rad Biol Med, AJP, AJM all describing the function of myeloperoxidase and reactive oxygen and nitrogen species as being particularly impactful. He has been NIH funded for decades with an R21 recently completing in 2013. Perhaps most important to our division, Dr. Cross wrote our original T32 Comparative Lung Biology Training Grant and served as PI and Co-PI for over 30 years (Grant # 7033 from NHLBI!). This grant has trained numerous faculties in the medical school and veterinary school at UC Davis and beyond. This alone would be a career-worthy accomplishment.
In summary, he is an outstanding mentor to many faculty in the division even after year 40 as faculty. He has been our translational research leader for decades, long before the term was defined.
Nicholas Kenyon, M.D.
Professor of Medicine
Chief, Division of Pulmonary, Critical Care, Sleep Medicine
Congratulations Dr. Valentina Medici, recipient of the 2015 Internal Medicine Faculty Research Award!
After her graduation summa cum laude with the MD degree from the prestigious University of Padova in 2000 and subsequent fellowship training in Gastroenterology and Hepatology in Germany, Dr. Medici returned to the University of Padova where she began her research on the pathogenesis and management of Wilson disease (WD). This resulted in 8 publications of which she was first author on 5, that were clinical except for 3 that involved rat models of hepatic copper overload. Subsequently she moved to our institution in 2006 to become a visiting Assistant Professor and K30 scholar in our Mentored Clinical Scientist Development Award. Her subsequent research has focused on two areas of alcoholic liver disease (ALD) and WD.
Alcoholic liver disease: As a K30 scholar, she obtained her clinical research training under my direction in an NIH funded study of S-adenosylmethionine (SAM) in the treatment of ALD. In addition to the rigorous double blind clinical study (14 in her Biosketch), she made an original observation that the transsulfuration pathway of methionine metabolism was specifically compromised in ALD (1). A subsequent study in a mouse model of ALD confirmed the ethanol induction of changes in liver methionine metabolism with resultant reduction of the primary methyl donor SAM and reduced gene-specific DNA methylation with increased gene expression of inducible nitric oxide synthetase (iNOS), a known pathway for liver injury (4). Summarizing, these translational studies have confirmed and provided a mechanism for ethanol induced altered hepatic methionine metabolism in the pathogenesis of alcoholic liver injury and disease.
Wilson disease: While identifying altered hepatic methionine metabolism in ALD, she made the highly original connection that similar mechanisms could be operative in the pathogenesis of WD, a rare congenital disease of copper overload of the liver and the topic of all her prior research in Italy. This hypothesis and subsequent research led to successful acquisition of a prestigious NIH K08 new faculty development and later R03 awards. Her studies first demonstrated the association of hepatic copper overload with enhanced levels of S-adenosylhomocysteine (SAH), a primary inhibitor of gene methylation, whereas copper reduction or provision of the alternate methyl donor betaine restored global DNA methylation while increasing SAM and reducing a gene pathway for liver necrosis and inflammation (2). A subsequent mechanistic study showed parallel changes over time from fetal life to adulthood of copper accumulation, reduced SAH hydrolase transcripts, enhanced SAH levels with reduced DNA methylation (5). A third study demonstrated the epigenetic generational transmission of WD by finding that maternal provision of the methyl donor choline could prevent many of the transcriptional defects in WD fetal and 28 d old livers while enhancing global DNA methylation in the same mouse model (3). These studies form the basis of a current NIH R01 application which will further explore epigenetic effects of methyl donors in potential prevention and treatment of WD.
Charles H. Halsted, MD
Congratulations Dr. Tonya Fancher
Congratulations Dr. Tonya Fancher! Dr. Fancher is the recipient of the 2014-2015 Chancellor's Achievement Award for Diversity and Community.
Congratulations Dr. Sanket Dhruva!
Sanket Dhruva, M.D. (PGY-6, cardiology) was recently accepted to become a Robert Wood Johnson Clinical Scholar at Yale University from 2015-2017. During medical school and internal medicine residency training at UCSF, he studied FDA regulation and Medicare coverage of medical devices. His work has been published in the New England Journal of Medicine, JAMA, and the British Medical Journal. During his cardiology fellowship at UC Davis, he has gained a better understanding of how devices are used to better the health of patients with cardiovascular disease and hopes to use the two-year clinical scholars program as a transition to an academic career.
Congratulations to the Division of Cardiovascular Medicine!
- Nipavan Chiamvimonvat, M.D. received a VA Merit Review Award, "Regulation of ion channels in the heart." Project Period: 10/01/2014 - 09/30/2018; Amount: $650,000
- Javier Lopez, M.D. received a K12 award, “Predicting cardiac recovery after myocardial infarction: building a new quantitative EMR-based and microRNA expression prediction model” funded through CTSC. Project Period: 07/01/14 - 06/30/16; Amount: $200,000
- Ye Chen-Izu, Ph.D. is the recipient of the Grant-in-Aid “Mechano-chemotransduction underlying mechanical stress induced arrhythmias,” from the American Heart Association (AHA) Project Period: 07/01/14 - 06/30/16 $140,000
- Xiaodong Zhang, Ph.D. was awarded the Beginning Grant in Aid “Novel mechanisms for the regulation of acid –base balance in cardiac myocytesin" from the American Heart Association (AHA). Project Period: 01/01/14 - 12/31/15; Amount: $140,000
- John Rutledge, M.D. received an Opportunity Grant “Assessment of cognitive function in mouse metabolic models” through the NIH-sponsored National Mouse Metabolic Phenotypic Center (MMPC). Project Period: 2014 - 2015; Amount: $162,000
- The NIH T32 grant "Training Program in Basic and Translational Cardiovascular Sciences" has been renewed for another five years. Co-Program Directors: Nipavan Chiamvimonvat, M.D. and Ann Knowlton, M.D. Project Period: 07/01/2013 - 06/30/2018; Amount: $2,050,000
- Nipavan Chiamvimonvat, M.D. was the recipient of a NIH S10 Shared Equipment Grant "In vivo ultrasound imaging system," (VisualSonics Vevo2100). Amount: $400,000
- Nipavan Chiamvimonvat, M.D. published a paper "Functional interaction with filamin A and intracellular Ca2+ enhance the surface membrane expression of a small-conductance Ca2+-activated K+ (SK2) channel" in Proceedings of the National Academy of Sciences (PNAS). Click on the link to view the article http://www.pnas.org/content/111/27/9989.full.pdf+html
- Ann Knowlton, M.D. received the 2013 Albrecht Fleckenstein Memorial Award for her distinguished work in the field of basic research from the International Academy of Cardiology. Click on the link to view press release https://www.ucdmc.ucdavis.edu/publish/awards/aboutus/8081/?p=index.html
Research Spotlight on Amir A. Zeki, M.D.
Dr. Amir Zeki's research interest is broadly in the area of metabolic and lipid regulation of chronic inflammation and remodeling in the lung. More specifically, he has studied the mevalonate pathway in lung biology. “This is the same pathway that controls cholesterol biosynthesis and regulates the location and function of the small G-proteins (GTPases) which are important cell signaling proteins. The statin drugs (known as the ‘cholesterol-lowering’ drugs) target this pathway and are increasingly being appreciated to have significant anti-inflammatory effects in many tissues beyond the cardiovascular system. In addition to lowering cardiovascular mortality, there is some suggestion that they may also have benefits in lung health, e.g. asthma and COPD.” He is also interested in determining which of the statins and by which route of administration could have the greatest benefit in lung disease.
Dr. Zeki’s translational research interest is in developing novel or innovative therapeutics for airway diseases such as asthma or COPD, two of the most common and costly lung diseases worldwide. “I have focused on investigating whether or not the statin drugs can mitigate chronic inflammation in asthma and COPD. My mentor, collaborators, and I have used animal models, in vitro cell culture systems, and clinical investigations to find answers.” He is currently the Principal Investigator of the first randomized clinical trial to evaluate whether simvastatin can reduce acute asthma exacerbations, improve lung function, and reduce chronic allergic airway inflammation in patients with severe asthma. In the near future, he plans to develop the statins as a novel inhaler for targeted airway application to maximize their airway/lung effects.
Most recently, he has developed an interest in cell fate phenomena such as endoplasmic reticulum (ER) stress/unfolded protein response, autophagy, and apoptosis as they relate to disease pathogenesis in severe asthma, COPD, and lung fibrosis. Dr. Zeki’s favorite collaborative work is with Dr. Saeid Ghavami at the University of Manitoba, in Winnipeg, Canada. Drs. Zeki and Ghavami are exploring the role of autophagy in asthma. ‘Autophagy’ is a fundamental cellular process, an adaptive intracellular and lysosome-dependent degradation mechanism necessary for cell survival, recycling of cellular components, and maintenance of homeostasis. Autophagy also has the potential to promote cell death, and thus is a critical cellular event that controls cell fate in different organs. Its role in airway diseases remains a mystery. Dr. Zeki and his colleague have ongoing collaborative experiments to determine whether or not autophagic responses are mediating pro-inflammatory cytokine release and pro-fibrotic responses in airway epithelial and mesenchymal cells, respectively. They believe these events mediate adverse airway structural remodeling leading to persistent symptoms in patients with severe asthma. Interestingly, there is also cross-talk between the mevalonate pathway and autophagy revealing potentially novel pleiotropic effects of the statins.
When Dr. Zeki was asked why he loves research, he responeded “I see no barriers, no real differences between the curiosity that a clinician or scientist has, and the effort it takes to find answers to challenging questions. Both involve inquiry and a process to find the right answers. Research is a natural human impulse as one contends with mysterious phenomena in life. The scientific method which underpins basic or clinical research is simply a tool to find the best answers possible. This requires a skill set different from the typical training that a physician receives. However, the spirit of that pursuit is the same in my mind. The decision to do research as part of my career path is rooted in a passion to investigate problems that could have a clinical impact. Research is a practical response to the questions that arise from the clinical realm. In truth, despite its many challenges, risks, and failures, research is also fun and personally rewarding.”
Recent Grants and Awards
Department of Internal Medicine 2014
Faculty Research Award
Western American Federation for Medical Research (AFMR) 2013-2014
Outstanding Investigator Award
American Federation for Medical Research (AFMR) 2012
Henry Christian Award
NIH/NHLBI K08 Award (PI: A Zeki) 01/01/14 – 1/31/17
The Modulation of Eotaxin Expression by Statins: Implications for Asthma Therapy
To understand the mechanisms by which statins regulate gene expression of the eotaxins, potent eosinophil chemokines, and in doing so elucidate general underlying principles of the statin effect on a wider array of genes involved in TH2 lung inflammation relevant to allergic asthma and COPD. Aim 3 is a cross-over clinical trial to evaluate whether simvastatin added to inhaler therapy can reduce asthma exacerbations in patients with severe asthma.
Tobacco-Related Disease Research Program (PI: B. Davis) 07/01/09 – 06/30/13
Novel Treatments for COPD with Statins
To investigate whether tobacco smoke-induced chronic lung inflammatory and structural changes correlate with pulmonary function measurements in a model of spontaneously
hypertensive rats, and whether treatment with statins can mitigate COPD pathogenesis.
American Thoracic Society (PI: A Zeki) 07/01/09 – 06/30/10
Fellows Career Development Award
The Role of Statins in Modulating Airway Hyperreactivity and Remodeling
To determine the mechanisms whereby statins modulate asthmatic inflammation, airway hyperreactivity, and airway remodeling.
Yeganeh B, Wiechec E, Ande SR, Sharma P, Moghadam AR, Post M, Freed DH, Hashemi M, Shojaei S, Zeki AA, Ghavami S. Targeting the mevalonate cascade as a new therapeutic approach in heart disease, cancer and pulmonary disease. Pharmacol Ther. 2014 Feb 26. [Epub ahead of print]
Zeki AA. Statins and asthma: where we stand, and the next critical steps in research.
Curr Med Res Opin. 2014 Jan 30. [Epub ahead of print]
Zeki AA, Oldham J, Wilson M, Fortenko O, Goyal V, Last M, Last A, Patel A, Last JA, Kenyon NJ. Statin Use and Asthma Control in Patients with Severe Asthma. BMJ Open. 2013 Aug 13;3(8).
Kenyon NJ, Bratt JM, Lee J, Luo J, Franzi LM, Zeki AA, Lam KS. Self-assembling nanoparticles containing dexamethasone as a novel therapy in allergic airways inflammation.
PLoS One. 2013 Oct 25;8(10):e77730.
Davis BB, Zeki AA, Bratt JM, Wang L, Filosto S, Walby WF, Kenyon NJ, Goldkorn T, Schelegle ES, Pinkerton KE. Simvastatin Inhibits Tobacco Smoke-Induced Acute Lung Inflammation and Airway Injury: Implications for the Treatment of COPD. Eur Respir J. 2013 Aug;42(2):350-61.
Zeki AA, Thai P, Kenyon NJ, Wu R. Differential Effects of Simvastatin on IL-13-Induced Cytokine Gene Expression in Mouse Primary Tracheal Epithelial Cells. Respir Res. 2012 May 14;13:38.
Zeki AA, Bratt JM, Rabowsky M, Last JA, Kenyon NJ. Simvastatin Inhibits Goblet Cell Hyperplasia and Lung Arginase in a Mouse Model of Allergic Asthma: A Novel Treatment for Airway Remodeling? Transl Res. 2010 Dec;156(6):335-49.
Zeki AA, Franzi L, Last J, Kenyon NJ. Simvastatin Inhibits Airway Hyperreactivity: Implications for the Mevalonate Pathway and Beyond. Am J Respir Crit Care Med. 2009 Oct 15;180(8):731-40.
RESEARCH SPOTLIGHT ON JAY V. SOLNICK, M.D., PH.D.
In 1993, while an Infectious Disease fellow at Stanford University, Dr. Solnick had the opportunity work in the laboratory of Dr. Agnes Labigne at the Pasteur Institute in Paris. "At the time, she was the only scientist in the world who was able to genetically manipulate Helicobacter pylori, and I went there to learn how. The work was hard and the initial results were disappointing. Agnes told me that 'the most important lesson I ever learned in my scientific career was just keep going'. I did, the experiments eventually worked, and I never forgot this lesson, which I have repeated to my students many times."
Dr. Solnick’s lab has been funded by the NIH since shortly after his arrival at UC Davis in 1995. "The funding climate at NIH has become extraordinarily difficult, and even very accomplished investigators are finding themselves without NIH support. I was very gratified recently to learn that our most recent R01 application was scored in the top 2%, which assures that we will be able to continue our work for another 5 years."
Dr. Solnick’s laboratory studies Helicobacter pylori, a bacterial pathogen that commonly infects the human stomach and sometimes leads to peptic ulcers or gastric cancer. They use mouse and non-human primate models, as well as in vitro cell culture, to understand how H. pylori causes disease. They also perform translational studies. For example, his lab recently led an international collaboration to use mass spectrometry to identify serum glycans that might identify those H. pylori-infected patients who are at increased risk of gastric cancer.
His lab recently discovered a novel strategy that H. pylori uses to dial up or dial down its capacity to cause inflammation—a sort of "molecular rheostat" that tunes the host response, presumably for the benefit of the pathogen. "The implication is that inflammation, the host response to control infection, is actually co-opted to serve the interests of the bacterium. They aren’t as smart as we are, but there are a lot more of them, and there is strength in numbers!"
Dr. Solnick enjoys exercising in the morning and rides his bike everywhere that he can. He also enjoys working in the garden, cooking, and playing the guitar. "My wife and I recently bought a small cabin in Mt. Shasta, and we love to hike with our devoted golden retriever, Cooper. I also have a longstanding interest in learning Spanish, which began as a medical student working in Spanish Harlem in New York. I attend a weekly conversation class at the International House in Davis and try to do the homework when I have time."
Ozcan S, Barkauskas DA, Ruhaak LR, Javier Torres J, Cooke CL, An H, Hua S, Williams CC, Dimapasoc LM, Kim J, Camorlinga-Ponce M, Rocke DM, Lebrilla C, Solnick J.V. Serum glycan signatures of gastric cancer. Cancer Prev Res, 2013 Dec 10. [Epub ahead of print]
Moore ME, Lam A, Bhatnagar S, Solnick JV. Environmental determinants of transformation efficiency in Helicobacter pylori. J Bacteriol. 2014 Jan;196(2):337-44. doi: 10.1128/JB.00633-13.
Martin, ME, Bhatnagar, S, George, MD, Paster, BJ, Canfield, DR, Eisen, JA, and Solnick, JV. The impact of Helicobacter pylori infection on the gastric mic robiota of the rhesus macaque. 2013, PLoS ONE 8(10): e76375.
Cooke CL, Torres J, Solnick JV. Biomarkers of Helicobacter pylori-associated gastric cancer. Gut Microbes. 2013 Jul 12;4(6).
Barrozo, RM, Cooke, CL, Hansen, LM, Lam, AM, Gaddy, JA, Johnson, EM, Cariaga, TA, Suarez, G, Peek, RM Jr, Cover, TL, and Solnick, JV. Functional plasticity in the type IV secretion system of Helicobacter pylori. PLoS Pathogens, 2013, Feb;9(2):e1003189. Reviewed in Faculty of 1000
Martin, ME, Dieter, JA, Luo, Z, Baumgarth, N and Solnick, JV. Predicting the outcome of infectious diseases: Variability among inbred mice as a new and powerful tool for biomarker discovery. mBio, 2012 Oct 16;3(5):e00199-12.
Jay V. Solnick, M.D., Ph.D.
Professor of Medicine and Microbiology and Immunology
Department of Internal Medicine
Division of Infectious Diseases
Staff Scientist, California National Primate Research Center
Core Faculty Member, Center for Comparative Medicine
Research Funding News
American Federation for Medical Research
The AFMR works to support the careers of academic physician-scientists and to develop and encourage young academic and clinical researchers. Some of the ways that the AFMR works toward this mission are Professional Opportunities and Advocacy.
Additional benefits for your residents and fellows are the opportunity to present their research at a regional meeting and be eligible to apply for travel and trainee awards. Many of the academic leaders in our region attend this meeting so it is an excellent opportunity for your trainees to network as they are looking for a fellowship or faculty position. It is also an excellent chance for mentees and mentors to attend the meeting together to showcase their work. We hope you will accept our invitation to attend this meeting and encourage your faculty and trainees to submit abstracts and attend the meeting in Carmel, CA.
Please note the call for abstracts deadline is October 1, 2013. For details: http://bit.ly/14gBxf3
Furthermore, please connect with us through the AFMR LinkedIn Group, and join our Discussion Forum here: http://linkd.in/14gAxrc.
CALL FOR FELLOWSHIP APPLICATIONS:
Eligibility: Graduate students, postdoctoral fellows, and medical students and residents at member MMPC institutions
Requirements: One-page abstract application; Poster presentation on the day of the Symposium
Fellowship: Will support travel expenses and poster presentations up to $1,500
Deadline: 5PM PT, September 27, 2013. Please send the one-page abstract to Sasha Wirth (SSWirth@ucdavis.edu)
November 8, 2013
7:30 AM-12 Noon
AGR Hall, Buehler Alumni & Visitor Center