The UCLA Department of Anesthesiology and Perioperative Medicine is a consistent leader in patient care and research on all frontiers: basic science, clinical, and translational research. Our faculty members are top recipients of NIH awards, and continuously strive to enrich the clinical, educational, and research mission of the department.
While clinical research has always partnered with patient care, the potential for the field of anesthesiology to achieve great progress in basic science and translational research has not always been as clear. But as Yibin Wang, PhD, sees it, those days are over. Dr. Wang, our Vice Chair for Research and Director of the Division of Molecular Medicine, recently characterized the department’s research progress as “turning a pipe dream into a pipeline” for outside funding, laboratory expansion, and major research accomplishment.
Please visit our Basic and Translational Research web page to learn more about our renowned research laboratories and the many awards and grants received by our principal investigators. Several of the laboratories have their own websites with more in-depth information about their ongoing work.
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UCLA Health has created a new institute for precision medicine, a key piece of a larger precision health venture within the UCLA Clinical and Translational Science Institute (CTSI). Our department has become a vital partner in the implementation of this program, particularly in the realm of cardiovascular precision medicine.
Each patient who presents to our preoperative assessment clinic or is admitted for same-day surgery is asked to donate a blood sample to be used for genomic analysis. The sheer size and diversity of the UCLA health system will provide the resources necessary to collect and preserve the samples, store large data files, and link high-powered genetic analysis of the samples with outcomes data from our electronic health record system. Our research laboratories are developing computational tools for the analysis of genetic data in order to facilitate the study of complex conditions such as cancer, rheumatoid arthritis, and cardiovascular disease.
As perioperative physicians, we face new challenges to patient care in an era of constrained resources, more procedures needed by patients with complex and critical illnesses, and an aging population. Genomics has the potential to provide us with the tools necessary to anticipate how each individual patient will respond to the numerous stresses and pharmacological exposures of the perioperative period. We will be able to study the responses of patients with different genetic subtypes to commonly used pain medications, anesthetics, antihypertensive medications, and anticoagulants. If we can understand the contribution of the genetic makeup to the outcomes of our patients, we will truly be able to personalize their care, choosing the best medication every time.
Researchers in precision medicine expect to find that patients will fit into different genomic categories. The goal is to use the preoperative blood samples, together with tissue samples collected at the time of surgery, to identify groups of patients at particular risk for complications such as stroke, myocardial infarction, acute kidney injury, bleeding, arrhythmias, cognitive decline, and sepsis. Once the genetic variants are identified, the data can be used to develop better care strategies, including the appropriate preoperative medical management, degree of surgical invasiveness, plan for intraoperative anesthesia, and level of post-operative care.
Anesthesiologists face a major challenge in assimilating genomic information into the current model of perioperative health care. There is tension between the concepts of standardized protocols for efficient, high-quality healthcare and individualized care via precision medicine. Our faculty members have discussed this concept in a lead article in Anesthesia & Analgesia, titled “Standardized Care Versus Precision Medicine in the Perioperative Setting.”
Our department believes there is great promise in overcoming these challenges and providing even better care to our patients. We are proud to play a pivotal role in developing precision health care at UCLA as we acknowledge the tremendous impact of genomics on the future of medicine.
Grants from UCLA's Clinical and Translational Science Institute (CTSI) support the study of two major cardiac problems that affect thousands of patients: pulmonary hypertension and atrial fibrillation. Our department's investigators have identified a key molecule that controls the production of oxidized lipids, and is reduced in the lungs and blood of patients with pulmonary hypertension. They hope to develop a new blood test that can aid early detection. Other research is studying how changes in genetic material over time correlate with disease incidence and progression. Specifically, his team is looking at DNA methylation, and how this marker may predict the severity of atrial fibrillation in response to an environmental stress.
One of our junior faculty researchers, Kimberly Howard-Quijano, MD, MS, has won a Foundation for Anesthesia Education and Research (FAER) grant to study sudden cardiac death and ventricular tachyarrhythmias. Working in the laboratory of Aman Mahajan, MD, PhD, our department chair, Dr. Howard and her colleagues are studying imbalances in the nervous system that are known to play a large role in triggering these arrhythmias. Surprisingly, interventions that affect the spinal cord – such as spinal cord stimulation and epidural anesthesia – may be therapeutic for cardiac arrhythmias. Working with normal subjects first, and then with patients who have suffered heart attacks, this research studies the effect of spinal cord stimulation on heart rhythms to expand understanding of how spinal neuromodulation therapies work. A recent study demonstrated in a porcine model how thoracic epidural anesthesia attenuates ventricular myocardial excitability and induces electrical wave stability.
Another of our newest faculty members, Soban Umar, MD, PhD, is the winner of a FAER Mentored Research Training Grant to study idiopathic pulmonary fibrosis (IPF), a progressive disease with a poor prognosis that often leads to a need for lung transplantation. IPF patients who develop pulmonary hypertension have even worse outcomes. Dr. Umar and his mentors, Aman Mahajan, MD, PhD, and Mansoureh Eghbali, PhD, have developed the first model of combined pulmonary fibrosis and pulmonary hypertension in rats, effectively simulating the human disease. Their goal is to devise a novel therapy, specifically studying a molecule called microRNA 125b-3p. This molecule may serve as a biomarker for disease progression, and may also serve as a therapeutic target for treatment.
The work of other renowned and prolific researchers in our department centers on molecular regulation of the cardiovascular protective enzyme endothelial nitric oxide synthase (eNOS), and its contributions to cardiovascular diseases of increased reactive oxygen species production. The goal of this research is to delineate details of eNOS regulation in an oxidant stress environment, which may lead to novel therapeutics targeting an array of cardiovascular disorders including hypertension, atherosclerosis, diabetic vascular diseases, heart failure, and the biological process of aging. Ongoing projects also investigate oxidant stress mechanisms in human atrial fibrillation, the role of vascular oxidative stress in obesity, and novel therapeutics to eliminate the cardiovascular side effects of cancer drugs. Other research focuses on genetic and molecular mechanisms of heart failure and metabolic disorders. Major advances have been made in uncovering stress-signaling mechanisms in the pathogenesis of heart failure, revealing the functional importance of amino acid catabolism in heart failure and metabolic disorders.
Andrew Hudson, MD, PhD, has received a prestigious grant from the National Institute of General Medical Sciences to study the impact of anesthetics on the nervous system, with the longer-term goal of understanding how recovery of consciousness from anesthesia occurs. Using a mouse model, Dr. Hudson is investigating how individual neuron populations within the brain cortex show changes in electrical activity at different anesthetic depths. His research model causes the neurons to fluoresce when they are stimulated. By selectively targeting and intervening in these neuron populations, Dr. Hudson’s work investigates changes in the brain that lead to unconsciousness from anesthesia, and the resulting recovery of consciousness after anesthesia.
Rajesh Kumar, PhD, studies the neural control of autonomic, breathing, and cognitive function. His laboratory uses magnetic resonance spectroscopy and various MRI procedures to assist in the localization of abnormal brain regions, and to assess neural activity in patients with obstructive sleep apnea (OSA) and heart failure. Patients with heart failure show brain injury in autonomic, mood, and cognitive regulatory areas. The research team has also studied injury to different types of white matter (axonal or myelin injury), and showed that heart failure subjects exhibit more neural damage than do OSA patients, particularly in brain areas that serve memory and mood functions. Dr. Kumar's lab seeks to determine the onset of the neural damage in heart failure and OSA, the specific cardiovascular or breathing effects that result from neural damage, and the extent of progression as the syndromes continue. These findings could lead to preventive measures before severe, long-term consequences ensue, such as hypertension, stroke, and daytime hypersomnia in OSA patients, and autonomic, mood and cognitive deficits in heart failure patients.