Recipient of the 2022 Alumni Trailblazer Award

Dr. Joseph W. Turek, MD, Ph.D., MBA is an academic pediatric cardiac surgeon at Duke University in Durham, North Carolina. Since 2017, Dr. Turek has served as chief of pediatric cardiac surgery and executive co-director of Duke Children’s Pediatric & Congenital Heart Center. Prior to Duke, he served in a similar leadership role at the University of Iowa Stead Family Children’s Hospital from 2012-2017. A native of Petersburg, Illinois, Dr. Turek attended IMSA in the second graduating class. He then graduated from Northwestern University with a degree in biochemistry and received his M.D./Ph.D. (pharmacology) from the University of Illinois in Chicago with Alpha Omega Alpha distinction. He completed his general surgery education at Duke University, where he also finished a cardiothoracic surgery residency. During this time, he served as a visiting congenital heart surgery fellow at Texas Children’s Hospital. Dr. Turek completed a congenital cardiac surgery fellowship at the Children’s Hospital of Philadelphia in 2011. He received his MBA with a concentration in Health Sector Management from Duke’s Fuqua School of Business in 2020. Board certified in general surgery, thoracic surgery, and congenital cardiac surgery, Dr. Turek has been one of the foremost innovators of the last decade in congenital heart surgery, developing novel operations, modifying techniques, and introducing new products and procedures to children and adults with congenital cardiac disease. Most notably, he performed the world’s first co-transplant of a heart and cultured thymus tissue in an operation that could usher in an era in which solid organ transplant recipients can develop tolerance to their newly transplanted organ, recognizing them as “self”. In another highly innovative operation, he performed the world’s first partial heart transplant for a newborn without functioning aortic or pulmonary valves, maintaining growth capacity of the newly implanted valves. Additionally, he led the team at Duke in completing the nation’s first pediatric donation after circulatory death heart transplant with ex vivo reanimation as a means to expand the already limited donor pool of available organs. His clinical passion and expertise lies in high complexity neonatal heart surgery. Academically, Dr. Turek has published over 150 peer-reviewed manuscripts and book chapters. He maintains an active and well-funded research laboratory with projects spanning from basic science to translational to clinical research, in areas such as heart transplantation tolerance, living root transplantation, miniaturized ventricular assist devices, Marfan syndrome, and the role of alpha-gal sensitization in biologic valve degradation. He maintains active leadership roles in national and international cardiothoracic surgery societies

Circadian Disruption and Metabolic Disease: Findings from Animal Models

Social opportunities and work demands have caused humans to become increasingly active during the late evening hours, leading to a shift from the predominantly diurnal lifestyle of our ancestors to a more nocturnal one. This voluntarily decision to stay awake long into the evening hours leads to circadian disruption at the system, tissue, and cellular levels. These derangements are in turn associated with clinical impairments in metabolic processes and physiology. The use of animal models for circadian disruption provides an important opportunity to determine mechanisms by which disorganization in the circadian system can lead to metabolic dysfunction in response to genetic, environmental, and behavioral perturbations. Here we review recent key animal studies involving circadian disruption and discuss the possible translational implications of these studies for human health and particularly for the development of metabolic disease

Circadian Timing of Food Intake Contributes to Weight Gain

Studies of body weight regulation have focused almost entirely on caloric intake and energy expenditure. However, a number of recent studies in animals linking energy regulation and the circadian clock at the molecular, physiological, and behavioral levels raise the possibility that the timing of food intake itself may play a significant role in weight gain. The present study focused on the role of the circadian phase of food consumption in weight gain. We provide evidence that nocturnal mice fed a high‐fat diet only during the 12‐h light phase gain significantly more weight than mice fed only during the 12‐h dark phase. A better understanding of the role of the circadian system for weight gain could have important implications for developing new therapeutic strategies for combating the obesity epidemic facing the human population today

Towards Multi-Modality Therapy for Marfan Syndrome: Synergistic Effect of Angiotensin and TRPC4 Receptor Blockade on Ascending Aortic Aneurysms

Background: Marfan syndrome (MFS) is a genetic disease that commonly presents with aortopathy. While promising therapies have been studied, complete attenuation of MFS-induced aortic aneurysms in the clinical arena has been elusive. The presence of significant, not-yet described MFS signaling pathways has been suggested as a reason for the less than ideal clinical response to single drug therapy. Transient receptor potential (TRP) channels have emerged as likely regulators of vascular smooth muscle cell (VSMC) activity. In this regard, they are abundantly found in VSMCs and are associated with increased matrix metalloproteinase 9 activity. The current study seeks to explore the role of TRP channels in MFS. Methods: A Fbn1C1039G/+ heterozygous mouse, with a mutation in fibrillin-1, was supplemented with angiotensin II (4.5 mg/kg/day) to accelerate aneurysmal formation. Mice analyzed were wild type (wt) (saline +/- angiotensin II) and heterozygous (saline +/- angiotensin II). Quantitative PCR and western blotting was used to examine differential expression of TRP channels across the various cohorts. The TRPC4 antagonist, ML204 (10mg/kg/day), was given daily during two weeks of angiotensin II infusion. Mice were echoed before and after to assess aortic diameter. Results: Quantitative PCR of the accelerated model revealed a near 10-fold increase in TRPC4 transcription with respect to wt mice. ML204 and losartan worked synergistically to ameliorate aortic dilation. Conclusions: These studies suggest a complementary role for TRPC4 in MFS-induced aortic pathology. Antagonism of this novel target shows promise toward multi-drug therapy for the treatment of aortic aneurysms in MFS

Phase shifting the circadian clock with cycloheximide : response of hamsters with an intact or a split rhythm of locomotor activity

Systematic administration of the protein synthesis inhibitor, cycloheximide, induced both phase advances and phase delays in the circadian rhythm of wheel-running activity in hamsters (Mesocricetus auratus) maintained in constant darkness or constant light. The magnitude and direction of the phase shifts were dependent on the circadian time (CT) of drug treatment. The phase response curves in constant darkness and constant light were of similar general shape, but they differed in the overall mean amplitude of the phase shifts. Maximal phase advances were observed after injections around CT 6-8, maximal delays at CT 0-2. Injections of various doses of cycloheximide at CT 0 induced a dose-dependent phase delay in the rhythm with a maximum delay induced by 10 mg cycloheximide. Injections of cycloheximide in animals with a split activity rhythm caused phase shifts of both components in the same direction (20/39) and in different directions (10/39). The results support the hypothesis that 80S ribosomal protein synthesis plays an important role in the biochemical mechanisms of circadian systems

Inhibitor of protein synthesis phase shifts a circadian pacemaker in mammalian SCN

The suprachiasmatic nucleus (SCN) of the hypothalamus contains a circadian pacemaker that regulates many circadian rhythms in mammals. Experimental work in microorganisms and invertebrates suggests that protein synthesis is required for the function of the circadian oscillator, and recent experiments in golden hamsters suggest an acute inhibition of protein synthesis can induce phase shifts in a mammalian circadian pacemaker. To determine whether protein synthesis in the SCN region is involved in the generation of circadian rhythms in mammals, a protein synthesis inhibitor, anisomycin, was microinjected into the SCN region, and the effect on the circadian rhythm of locomotor activity of hamsters was measured. A single injection of anisomycin into the SCN region induced phase shifts in the circadian activity rhythm that varied systematically as a function of the phase of injection within the circadian cycle. These results suggest that protein synthesis may be involved in the generation of circadian rhythms in mammals and that the anatomic site of action of anisomycin is within the hypothalamic suprachiasmatic region

Successful Heart-Liver Transplant Using Dual-organ Normothermic Perfusion in a Patient With Fontan Failure

Advances in surgical technique and multidisciplinary management have improved long-term survival for patients born with single ventricle physiology. However, patients who have undergone Fontan completion remain at risk for long-term comorbidities associated with the complex hemodynamic changes following the procedure, including Fontan failure and Fontan-associated liver disease.1 Combined heart-liver transplantation (CHLT) is a rare but lifesaving procedure that has been described in the setting of heart and liver failure secondary to Fontan failure.2 As long-term survival continues to improve for Fontan patients, the incidence of Fontan-associated liver disease will increase. Thus, improving CHLT outcomes and access to both organs is a strong priority. Here, we describe a successful CHLT for a patient with chronic ventricular dysfunction and Fontan-associated liver disease. The key innovation in this case was the use of normothermic machine perfusion (NMP) to preserve both the heart and liver grafts. This approach extended the preservation time for the liver while also mitigating the risk of ischemic injury and reducing the time pressure constraints on the heart transplant team. Notably, this stands in contrast to traditional static cold storage (SCS), where metabolic activity is reduced through hypothermia, but the extended cold ischemic time can lead to increased vulnerability to reperfusion injury

Uncovering the Genetic Landscape for Multiple Sleep-Wake Traits

Despite decades of research in defining sleep-wake properties in mammals, little is known about the nature or identity of genes that regulate sleep, a fundamental behaviour that in humans occupies about one-third of the entire lifespan. While genome-wide association studies in humans and quantitative trait loci (QTL) analyses in mice have identified candidate genes for an increasing number of complex traits and genetic diseases, the resources and time-consuming process necessary for obtaining detailed quantitative data have made sleep seemingly intractable to similar large-scale genomic approaches. Here we describe analysis of 20 sleep-wake traits from 269 mice from a genetically segregating population that reveals 52 significant QTL representing a minimum of 20 genomic loci. While many (28) QTL affected a particular sleep-wake trait (e.g., amount of wake) across the full 24-hr day, other loci only affected a trait in the light or dark period while some loci had opposite effects on the trait during the light vs. dark. Analysis of a dataset for multiple sleep-wake traits led to previously undetected interactions (including the differential genetic control of number and duration of REM bouts), as well as possible shared genetic regulatory mechanisms for seemingly different unrelated sleep-wake traits (e.g., number of arousals and REM latency). Construction of a Bayesian network for sleep-wake traits and loci led to the identification of sub-networks of linkage not detectable in smaller data sets or limited single-trait analyses. For example, the network analyses revealed a novel chain of causal relationships between the chromosome 17@29cM QTL, total amount of wake, and duration of wake bouts in both light and dark periods that implies a mechanism whereby overall sleep need, mediated by this locus, in turn determines the length of each wake bout. Taken together, the present results reveal a complex genetic landscape underlying multiple sleep-wake traits and emphasize the need for a systems biology approach for elucidating the full extent of the genetic regulatory mechanisms of this complex and universal behavior

Treatments for people who use anabolic androgenic steroids: a scoping review.

BACKGROUND: A growing body of evidence suggests that anabolic androgenic steroids (AAS) are used globally by a diverse population with varying motivations. Evidence has increased greatly in recent years to support understanding of this form of substance use and the associated health harms, but there remains little evidence regarding interventions to support cessation and treat the consequences of use. In this scoping review, we identify and describe what is known about interventions that aim to support and achieve cessation of AAS, and treat and prevent associated health problems. METHODS: A comprehensive search strategy was developed in four bibliographic databases, supported by an iterative citation searching process to identify eligible studies. Studies of any psychological or medical treatment interventions delivered in response to non-prescribed use of AAS or an associated harm in any setting were eligible. RESULTS: In total, 109 eligible studies were identified, which included case reports representing a diverse range of disciplines and sources. Studies predominantly focussed on treatments for harms associated with AAS use, with scant evidence on interventions to support cessation of AAS use or responding to dependence. The types of conditions requiring treatment included psychiatric, neuroendocrine, hepatic, kidney, cardiovascular, musculoskeletal and infectious. There was limited evidence of engagement with users or delivery of psychosocial interventions as part of treatment for any condition, and of harm reduction interventions initiated alongside, or following, treatment. Findings were limited throughout by the case report study designs and limited information was provided. CONCLUSION: This scoping review indicates that while a range of case reports describe treatments provided to AAS users, there is scarce evidence on treating dependence, managing withdrawal, or initiating behaviour change in users in any settings. Evidence is urgently required to support the development of effective services for users and of evidence-based guidance and interventions to respond to users in a range of healthcare settings. More consistent reporting in articles of whether engagement or assessment relating to AAS was initiated, and publication within broader health- or drug-related journals, will support development of the evidence base