Michael Sturek, Ph.D.
Professor, Department Chair
Department of Cellular & Integrative Physiology
Professor of Biomedical Engineering - Purdue BME
|Research (scroll down)|
Education / Training
- 1979, B.A. in Exercise Physiology, Psychology, Augustana College, Rock Island, Illinois
- 1980, M.S. in Exercise Physiology, Purdue University, West Lafayette, Indiana
- 1985, Ph.D. in Pharmacology, University of Iowa, Iowa City, Iowa
- 1987, Postdoctoral Fellowship in Membrane Physiology, University of Chicago, Chicago, Illinois
The general aim of our research program is to understand cellular and molecular Ca signaling mechanism for in vivo cardiovascular phenomena. Our research encompasses experimental approaches at all levels – clinical, whole animal, organ, tissue, cell, and molecular. Our clinical study in human diabetics on intravascular ultrasound imaging of coronary atherosclerosis guides our studies in swine that superbly mimic human atherosclerosis. We primarily study ion transport adaptations in cardiac and vascular endothelial and smooth muscle cells after several in vivo manipulations: 1) exercise training, 2) dyslipidemia, 3) metabolic syndrome (“pre-diabetes”), and 4) diabetes. Each condition requires chronic treatment of intact animals and study of isolated tissues and single cells from these animals. Our in vivo (whole animal) studies involve hemodynamic and insulin sensitivity measures. We are the only research group in the world with a breeding colony of Ossabaw swine that express metabolic syndrome, progression to type 2 diabetes, cardiac dysfunction, and profound atherosclerosis. We have characterized these swine extensively over the past ~14 years and provided Ossabaw widely beyond IUSM (e.g. Mayo Clinic), yielding a total of 106 published manuscripts. Organ level approaches utilize intravascular catheters, ultrasound, optical, and radiologic imaging, and localized gene targeting. Tissue level studies routinely involve culture of arterial segments and measurement of calcium and/or contraction. Typical cellular studies involve exposure of isolated cells to vasoactive agents in the metabolic syndrome and diabetic milieu (e.g. aldosterone), patch clamp electrophysiology, and fluorescence imaging. We have used multimodal nonlinear optical microscopy and vibrational photoacoustic imaging to characterize atherosclerotic lesions in our swine model. We are engineering catheters, drug delivery devices, and new compounds for early detection and treatment of diabetes and diabetes-induced complications. One molecular approach we use is to localize molecules within tissues and cells using several modes of microscopic imaging. With molecular cloning we have identified a novel adenosine A1 receptor, P2Y2 receptor, and TRPC channels that are regulated by several stressors and alter proliferation of coronary smooth muscle. We directly manipulate these potential molecular targets in vivo using drug-eluting stents and gene transfer via delivery catheters. A major goal is to prevent the progression of coronary smooth muscle Ca signaling from contractile to dedifferentiated proliferative, osteogenic, and apoptotic phenotypes in coronary disease. We have published more on coronary smooth muscle (CSM) intracellular Ca signaling and ion channels in health and in MetS/D over the past ~25 years than any group in the world. Our positron emission tomography-computed tomography (18F-NaF PET-CT) studies to image arterial calcification in vivo extend our Ca signaling studies further. I have 186 peer-reviewed publications (34 manuscripts in past 3 years) and trained 28 post-doctoral fellows, 18 PhD students, and 17 MS students in my laboratory.
Contribution to Science
Each of the 5 major contributions include 4 representative publications and are cited accordingly (e.g. 1a). Link to all: (https://scholar.google.com/citations?user=KNCraOIAAAAJ&hl=en.
1. Vascular smooth muscle (mainly coronary artery) Ca channel regulation
Nearly 30 years ago I was one of the first several vascular biologists in the world to characterize voltage-gated Ca channel subtypes using patch-clamp methods in freshly isolated vascular smooth muscle cells (1a, 1b). Electrophysiological characterization of voltage-dependence of channel gating and drug action in smooth muscle from several vascular beds provided fundamental knowledge that set the stage for understanding Ca influx and myoplasmic free Ca signaling and Ca localization in coronary smooth muscle. The chronic effects of exercise training, metabolic syndrome, and diabetic dyslipidemia on Ca-permeable channels coronary smooth muscle are a major emphasis of our laboratory (1c, 1d)
- Sturek, M., and K. Hermsmeyer. Calcium and sodium channels in spontaneously contracting vascular muscle cells. Science 233:475?478, 1986. PMID 2425434.
- Bean, B.P., M. Sturek, A. Puga, and K. Hermsmeyer. Calcium channels in muscle cells isolated from rat mesenteric arteries: modulation by dihydropyridine drugs. Circ. Res. 59:229, 235, 1986. PMID 2427250.
- Witczak, C.A., B.R. Wamhoff, and M. Sturek. Exercise training prevents Ca2+ dysregulation in coronary smooth muscle from diabetic dyslipidemic Yucatan swine. J. Appl. Physiol. 101:752- 762, 2006. PMID 16763107.
- Edwards, J.M., Z.P. Neeb, M.A. Alloosh, X. Long, I.N. Bratz, C.R. Peller, J.P. Byrd, S. Kumar, A.G. Obukhov, and M. Sturek. Exercise training decreases store-operated Ca2+ entry associated with metabolic syndrome and coronary atherosclerosis. Cardiovasc. Res. 85:631-640, 2010. PMID 197449.
2. Coronary smooth muscle sarcoplasmic reticulum Ca regulation
Imaging of myoplasmic free Ca with fluorescent probes (e.g. fura-2) at high time resolution (20 ms ratio intervals) with our custom-made instrumentation simultaneously with patch-clamp enabled demonstration of subsarcolemmal Ca localization due to Ca release from the sarcoplasmic reticulum (SR) (2a). Ca released spontaneously from the SR activated Ca-dependent K channels and also was extruded from the cell in a process we termed “SR Ca unloading”. The SR Ca store is precisely regulated at optimal levels by a dynamic balance of sequestration from the cytosol by the SR Ca ATPase pump (SERCA) and Ca release via ryanodine receptors (SR Ca release channels). Coronary smooth muscle SR Ca is modulated by several in vivo processes, including diabetes, exercise training (1c, 2c), insulin (2b), and other metabolic hormones such as glucagon-like peptide-1 (GLP-1) (2d). We now recognize the balance between SR Ca depletion that elicits “ER stress” and SR Ca overload that promotes CSM proliferation and migration. We have lead the field in coronary artery smooth muscle SR Ca regulation.
- Stehno Bittel, L., and M. Sturek. Spontaneous sarcoplasmic reticulum calcium release and extrusion from bovine, not porcine, coronary artery smooth muscle. J. Physiol. (Lond) 451:49- 78, 1992. PMID 1403820.
- Dick, G.M. and M. Sturek. Effects of a physiological insulin concentration on the endothelin- sensitive Ca2+ store in porcine coronary artery smooth muscle. Diabetes 45:876-880, 1996. PMID 8666136.
- Jones, J.J., N.J. Dietz, C.L. Heaps, J.L. Parker, and M. Sturek. Calcium buffering in coronary smooth muscle after chronic occlusion and exercise training. Cardiovasc. Res. 51:359-367, 2001. PMID 11470476.
- Dineen, S.L., M.L. McKenney, L.N. Bell, A.M. Fullenkamp, K.A. Schultz, M. Alloosh, N. Chalasani, and M. Sturek. Metabolic syndrome abolishes glucagon-like peptide-1 receptor agonist stimulation of SERCA in coronary smooth muscle. Diabetes 64:3321-3327, 2015. PMID 25845661. [See accompanying commentary: Davies, M.G. Diabetes 64:3066-3068, 2015. PMID 26294428]
3. Coronary smooth muscle Ca signaling and phenotypic modulation
A major functional outcome of altered CSM Ca signaling was the association with coronary atherosclerosis (3a) and CSM proliferation (3b). Nuclear Ca localization was tightly linked to localized SR around the nucleus, i.e. perinuclear SR and these Ca signaling processes were modulated by a lipid-lowering drug (atorvastatin) and exercise training (3a, 3b). We challenged dogma on the action of adenosine, which was long thought to be anti-mitogenic by showing that the adenosine A1 receptor subtype stimulated CSM proliferation (3c). We demonstrated again the phenomenal specificity of vascular smooth muscle, as adenosine was purely anti-mitogenic in aortic smooth muscle. We have published more on coronary smooth muscle (CSM) intracellular Ca signaling and ion channels in health and in MetS/D over the past ~25 years than any group in the world (3d for review)
- Wamhoff, B.R., J.L. Dixon, and M. Sturek. Atorvastatin treatment prevents alterations in coronary smooth muscle nuclear Ca2+ signaling associated with diabetic dyslipidemia. J. Vasc. Res. 39:208-220, 2002. PMID12097819 [Featured June 2002 in JVR internet discussion forum]
- Wamhoff, B.R., D.K. Bowles, N.J. Dietz, Q. Hu, and M. Sturek. Exercise training attenuates coronary smooth muscle phenotypic modulation and nuclear Ca2+ signaling. Am. J. Physiol. Heart Circ. Physiol. 283:H2397-H2410, 2002. PMID 12388302 [Journal cover photo January- March 2003]
- Shen., S.P. Halenda, M. Sturek, and P.A. Wilden. Cell signaling evidence for adenosine stimulation of coronary smooth muscle proliferation via the A1 adenosine receptor. Circ. Res. 97:574-582, 2005. PMID 16100051 [Journal cover photo September 16, 2005]
- Sturek, M. Ca2+ regulatory mechanisms of exercise protection against coronary artery disease in metabolic syndrome and diabetes. J. Appl. Physiol. 111:573-586, 2011. PMID 21596923.
4. Swine models of metabolic syndrome, diabetes, and coronary artery disease
Lack of suitable animal models of coronary artery disease (CAD) in MetS and diabetes (MetS/D) was previously a major obstacle. We have characterized MetS and diabetes in Yucatan and Ossabaw miniature swine, which superbly mimic human metabolism and CAD. In diabetic, dyslipidemic Yucatan pigs with early CAD the endothelin-sensitive SR Ca store in CSM was increased (4a) along with localized SR Ca release and ion channel modulation (4c). Although the Yucatan pig with the robust “diabetic milieu” continues to be useful, these pigs do not have primary insulin resistance. Thus, our integrated understanding of metabolism lead us to conduct an expedition to Ossabaw Island, GA to obtain Ossabaw miniature swine that have true insulin resistance and the entire constellation of metabolic syndrome (MetS) (4b, 4d).
- Lee , D.L., B.R. Wamhoff, L.C. Katwa, H.K. Reddy, D.J. Voelker, J.L. Dixon, and M. Sturek. Increased endothelin-induced Ca2+ signaling, tyrosine phosphorylation, and coronary artery disease in diabetic dyslipidemic swine are prevented by atorvastatin. J. Pharmacol. Exp. Ther. 306:132-140, 2003. PMID 12663685.
- Lee, L., M. Alloosh, R. Saxena, W. Van Alstine, B.A. Watkins, J.E. Klaunig, M. Sturek, and N. Chalasani. Nutritional model of steatohepatitis and metabolic syndrome in the Ossabaw miniature swine. Hepatology 50:56-67, 2009. PMID 19434740.
- Mokelke, E.A., Q. Hu, M. Song, L. Toro, H.K. Reddy, and M. Sturek. Altered functional coupling of coronary K+ channels in diabetic dyslipidemic pigs is prevented by exercise. J. Appl. Physiol. 95:1179-1193, 2003. PMID 12777409.
- Neeb, Z.P., J.M. Edwards, M. Alloosh, X. Long, E.A. Mokelke, and M. Sturek. Metabolic syndrome and coronary artery disease in Ossabaw compared with Yucatan swine. Comp. Med. 60:300-315, 2010. PMID 20819380.
5. Atherosclerosis imaging
We have done more imaging of CAD in swine with intravascular ultrasound (IVUS) than any group in the world (1d, 2d, 3a, 3b, 3d, 4a, 4c, 4d, 5c, 5d). The power in IVUS is that we characterize atherosclerosis in the entire coronary artery in vivo and then are able to dissociate CSM from localized sites for cellular and molecular Ca signaling studies. We have extended our imaging to 18F-NaF positron emission tomography-computed tomography (PET-CT) and a novel artery tracking analysis method that shows 18F-NaF uptake occurred in arteries with outward positive remodeling and early fatty streaks. We hypothesize that decreased SR Ca store (ER stress) results in release of exosomes and extracellular coronary artery calcification.
- Wang, H-W., I.M. Langohr, M. Sturek, and J-X. Cheng. Imaging and quantitative analysis of atherosclerotic lesions by CARS-based multimodal nonlinear optical microscopy. Arterioscler. Thromb. Vasc. Biol. 29:1342-1348, 2009. PMID 19520975. [Journal cover photo (Figure 4) September 2009]
- Wang, H-W. V. Simianu, M.J. Locker, J-X. Cheng, M. Sturek. Stent-induced coronary artery stenosis characterized by multimodal nonlinear optical microscopy. J. Biomed. Opt. 16:021110, 2011. PMID 21361673.
- Trask, A.J., P.S. Katz, A.P. Kelly, M.L. Galantowicz, M.J. Cismowski, T.A. West, Z.P. Neeb, Z.C. Berwick, A.G. Goodwill, M. Alloosh, J.D. Tune, M. Sturek, and P.A. Lucchesi. Dynamic micro- and macro-vascular remodeling in coronary circulation of obese Ossabaw pigs with metabolic syndrome. J. Appl. Physiol. 113:1128-1140, 2012. PMID 22837170.
- McKenney, M.L., P.R. Territo, A. Salavati, S. Houshmand, S. Persohn, Y. Liang, M. Alloosh, S.M. Moe, C.M. Weaver, A. Alavi, and M. Sturek. 18F-NaF positron emission tomography imaging of early coronary artery calcification. JACC Cardiovasc. Imaging (In press). PMID 26189122.
Overall description of our many research projects is found in the Global Description. The next section is Ossabaw Miniature Swine. Following that section are links to videos. Please allow several seconds for videos to play; longer if you are accessing this web page from a slower connection. More description of the content of videos is provided in the video tour below.
Global Description of Translational Medicine Research Program
Our translational medicine research rogram is described in the below document:
Ossabaw Miniature Swine – Centerpiece of the Comparative Medicine Program
The Comparative Medicine Program, which is a joint program of Purdue University and Indiana University School of Medicine represents tremendous interdisciplinary synergy and inter-institutional collaboration. Scientists at these universities have established the only research and large-scale breeding colony of Ossabaw swine in the world that is certified to have a gene mutation, the metabolic syndrome, and heart disease. The striking similarities between swine and human biochemistry, physiology, and pathophysiology provide outstanding opportunities for research in translational medicine. Ossabaw graphic--IU&PU Comp Med v14bib.pdf The Ossabaw Swine Resource is an officially designated Service Core in the Indiana Clinical and Translational Science Institute (CTSI; http://www.indianactsi.org/servicecores).
Overview and Tour of Purdue Ossabaw Facility
Overall Organization and Infrastructure
Resources for long-term housing and characterization of disease progression at the Purdue Ossabaw Facility are coordinated with extensive metabolic and cardiovascular phenotyping and interventions at IUSM.
Purdue Ossabaw Facility Standard Operating Procedures
Daily care of swine (feeding, watering, sanitation, healthcare), operation of the Facility, and biosecurity rules are described in detail in our Standard Operating Procedures (SOPs; SOP ASREC v10.pdf). Biosecurity agreements must be completed for visitors, veterinarians, and employees at our Facility. Ossabaw Swine Model of the Metabolic Syndrome
Brief description of the location and habitat of Ossabaw Island, GA provides a sound basis for the “thrifty genotype” of Ossabaw swine. The compelling need to preserve Ossabaw swine is presented. Please see also Sturek laboratory publications.
Finding the Perfect Pig
Dr. Sturek's undergraduate alma mater, Augustana College, provides an account of the expedition of Sturek and colleages to Ossabaw Island, Georgia to capture feral Ossabaw swine for use in biomedical research. Sturek Ossabaw Augustana Magazine S06.pdf [Used with permission from the Office of Communication, Augustana College, Rock Island, Ill. (http://www.augustana.edu).]
“PORKY PIGS On an island off Georgia, wild hogs developed many traits of human couch potatoes. Scientists are excited.” By Lawrence A. Armour. Fortune February 21, 2005. http://money.cnn.com/magazines/fortune/fortune_archive/2005/02/21/8251743/index.htm
Typical Design Of Chronic Studies
The well-characterized development of metabolic syndrome in Ossabaw miniature swine will enable determination of the mechanisms involved in the pathogenesis of metabolic syndrome, type 2 diabetes, and subsequent cardiovascular disease.
Information on animal cost, animals transportation, animal health status and contact information are shown in the following document
A typical “menu” of tissues available from Ossabaw studies is provided (Typical Ossabaw tissue v1.pdf). Exact tissue collection vials and persons wanting the tissues are provided for each tissue. For example, Adip.,Mesent.(AMES)1 in row 5 of the worksheet is collected in 1 x 50 mL centr tube and 4 x 1.5 mL tubes. A column labeled "Obtain?" is provided to make a checkmark after the tissue has been harvested. In that same row 5 is an open box in the column "Frozen" that is checked after the tissue has been placed in liquid nitrogen. The open box in the "Formalin" column in row 6 indicates that some of the mesenteric (visceral) fat is formalin fixed. Finally, for example, in row 7 the open box in the "Fresh" column and the note 2 indicates that some visceral fat is harvested for acute (fresh) use, in this case for dispersion of adipocytes by Dr. Spurlock. Investigators can peruse this “menu” of tissues and select tissues needed. Supply of coronary arteries is limited; however, for example, there is ample internal mammary artery and aorta. Another example is blood samples, which are provided fresh as indicated on line 29 by the open box in the fresh column and the name “March” in the NOTES column to designate that the tissue will be sent immediately to Dr. Keith March. We also have heparinized and EDTA-treated plasma samples. Thus, our system enables tissues to be provided fresh and preserved. Freshly harvested tissues are also shipped via overnight courier to investigators for use in physiological experiments on living preparations (e.g. C. Hardin, U. of Missouri).
Health Status of Closed Colony
Bordetella ..... vaccinated
Circovirus ...... vaccinated
E.coli ............. vaccinated (ProSystem CE)
Erysipelas ..... vaccinated
Ileitis ............ vaccinated
Influenza ...... vaccinated
Mycoplasma .. negative (never experienced a clinical disease outbreak since arrival to Purdue and have never heard a pig cough suggestive of mycoplasma)
Parvovirus .... vaccinated
Pasteurella ... vaccinated
PRRS ............. negative (negative upon arrival to Purdue)
Salmonella .... vaccinated (Argus SC/ST)
TGE ............... negative (negative upon arrival to Purdue)
Investigators Using Ossabaw Miniature Swine Resource
Tissues, data, and live swine have been provided to a total of 88 investigators in the period ~October 2005-January 2010, thanks to initial funding from NIH R24 RR013223 and R01 HL062552 and to continued funding from the Purdue-Indiana University School of Medicine Comparative Medicine Program. The principal investigators, institution, and tissue and/or data provided are shown in the table (Ossabaw Resource Utilization v13a.pdf). Note that over half of the investigators were from institutions other than our own institution, IUSM, thus indicating a broad availability of these tissues. Our wide distribution of resources clearly indicates our outstanding record and ability to manage this task that requires precise organization and diligence. We emphasize that live miniature swine have also been provided to investigators (Ossabaw Resource Utilization v13a.pdf). Our goal is to expand the availability and make investigators aware that work on a large animal is entirely feasible. We emphasize that the miniature size of the Ossabaw swine must be appreciated. The pigs are only ~30 kg at sexual maturity, thus studies in obese swine can be conducted on ~50-60 kg pigs. Our most outstanding example thus far of providing live swine is our shipment to Dr. David Flum at the University of Washington in Seattle. The pigs were first exposed to ~8-20 weeks of excess calorie atherogenic diet treatment to produce obesity in the pigs and we conducted intravenous glucose tolerance tests to verify insulin resistance before shipment. This maintains quality control of the obese metabolic syndrome phenotype. Further, transfer to U. of Washington was relatively straightforward and cost-effective by airplane shipment. Dr. Flum’s group is performing bariatric surgery on these pigs and the results are highly synergistic with ongoing research projects in the Comparative Medicine Program at IUSM and Purdue.
Policies For Tissue And Swine Distribution
Acknowledgement / Coauthor
As investigators receiving tissue and/or live swine prepare any abstract or manuscript for publication or poster for presentation, we ask that you acknowledge support from our NIH grants, which provided the tissues and/or pigs for the studies. Please use some citation like: "We acknowledge the support of NIH RR013223 and HL062552 to M. Sturek and the Comparative Medicine Center of IUSM and Purdue University for the Ossabaw swine / tissue." If you need any additional data regarding the metabolic status of the specific pigs from which the tissue was harvested or you need our interpretation of results, etc., then coauthorship with our group should be discussed. We appreciate your acknowledgement for the obvious reasons that we must provide documentation to granting agencies that our animal resource has provided useful materials for research projects. This is certainly a basis for future funding. Fees
We request shipping and handling fees to recover technician and administrator time required. Pricing for live swine is based largely on the age of pig and diet treatments. Please contact Mouhamad Alloosh for current pricing (email@example.com). Material Transfer Agreement
A standard Material Transfer Agreement (MTA) is required for distribution of tissues and a no breeding agreement for live swine. We process numerous MTAs very quickly, thus there is almost no delay in tissue and swine acquisition due to this step. Please review the MTA (Sturek template v2 MTA Ossabaw Pigs as Provider.doc) and contact Dr. Alloosh (firstname.lastname@example.org) to initiate the MTA . Advanced notice required for purchase of live swine
Since swine have nearly 4 months gestation and sexual maturity occurs at 5-6 months, acquisition of live swine requires advanced planning. Only a limited number of swine of ages ranging from neonate up to 12 months are available without prior scheduling. Please contact Mouhamad Alloosh for current availability (email@example.com). Please review our contact letter for phone contact numbers, more information on advantages of Ossabaw swine and uses in translational research, availability, cost, shipping, and additional services (glucose tolerance tests, angiography, etc.). Availability of tissues and live swine will depend on continued extramural funding and demand from investigators.
Description of the Video Tour
Both lean Yucatan pigs are exercising on a 2% treadmill grade at 3 mph during their aerobic training protocol. This rate is a fast walk/jog that increases heart rate and metabolism to levels that elicit increases in exercise capacity after chronic training. Ossabaw treadmill Rear View Waddle 3.mpg
Treadmill exercise of an obese Ossabaw pig after femoral artery ligation and coronary stent placement. Treadmill training is done with continuous monitoring of heart rate (belt around thorax) to monitor very carefully the exertion of the pig. The grade and speed of the treadmill are less than for lean pigs, but the exercise stimulus is sufficient to elicit an appropriate increase in heart rate. Angio in-stent stenosis.mpg
Post-stent angiogram shows a blood flow-limiting in-stent stenosis of left anterior descending coronary artery 4 weeks after stent deployment in Ossabaw miniature swine. Contrast media is infused through the guiding catheter arcing from the right and into the coronary ostium. A guidewire is in the left anterior descending coronary artery. The stenosis that is apparent during the injection of contrast media is shown by the arrow in Figure 2 in the "Global Description" file and is immediately distal to the first major diagonal branch off the left anterior descending artery. IVUS pullback severe atheroma.mpg
The video shows a pullback of the intravascular ultrasound imaging transducer 20-27 mm (shown 1/3 down from the top of the image on the left side) through the circumflex artery at a rate of 0.5 mm / second. It shows severe atheroma and several segments of nearly normal, healthy artery, e.g. 27.00 mm. EKG is superimposed on this recording, so that synchronization allows the determination of distensibility of the artery. IVUS pullback calcification.mpg
The video shows a pullback of the intravascular ultrasound imaging transducer 37-49 mm (shown 1/3 down from the top of the image on the left side) through the circumflex artery at a rate of 0.5 mm / second. Vascular calcification is noted at 8-9 o’clock at 39-42 mm into the pullback by the bright arcs with ultrasound signal dropout peripheral to the arcs. A large branch from the circumflex appears at 4-6 o’clock at 42-44 mm. in the pullback. Vascular calcification is also seen at 9-12 o’clock at 46-49 mm. The EKG is superimposed on this recording. IVUS pullback stent.mpg
The pullback of the intravascular ultrasound imaging transducer starting at 12 mm (shown 1/3 down from the top of the image on the left side) shows the ~3 mm diameter left anterior descending (LAD) artery distal to the stent. The metal stent is shown by the bright arcs at the perimeter of the artery clearly at 14 mm where the full deployment of the stent to a diameter of ~4 mm (1.3 times normal 3 mm diameter) is achieved to induce over-stretch injury of the artery. The most severe neointimal hyperplasia resulting from the injury is shown in a crescent moon-like shape at ~3-9 o'clock in the image at 14-17.5 mm medial to the bright arcs of the stent. The Ossabaw pig breed featured here is ideal for studies of restenosis after coronary stent placement. Adenosine-induced CBF.mpg
Cardiometrics FlowMap recording shows instantaneous peak blood velocity signals (middle envelopes) synchronized with the EKG (top) and blood pressure (next to top). Baseline data are recorded and then 1 (g adenosine/kg dose is given intracoronary via the guiding catheter at time 9:55:00 inducing an infusion artifact and then peak response at about 9:55:10. The increase in blood flow velocity is transient, recovering to baseline less than 25 seconds after the infusion. Nucleus fluo-4 mid-plane.mpg
A 3-dimensional reconstruction of nucleus (orange SYTO-64) and fluo-4 (green) shows confocal plane and the middle of the nucleus. This sampling is ideal for determination of nuclear calcium that is uncontaminated from cytosolic calcium. Nucleus fluo-4 out of plane.mpg
A 3-dimensional reconstruction of nucleus (orange SYTO-64) and fluo-4 (green) shows 2 confocal planes. The planes are above and below the nucleus and, thus, would not be used for determination of nuclear calcium. Computed tomography angio.avi
See the image (Computed tomography image.jpg) before starting the video to provide orientation to the features. The goal of this collaborative research lead by Drs. G. Kassab and S. Teague is to diagnose diffuse coronary artery disease by use of computed tomography (CT) imaging, which is less invasive than typically coronary angiography. High resolution, 64-slice CT collects images synchronized with the electrocardiogram. The contrast enhanced CT scan starts with a view from the anterior (A) position slightly from the left (L) of the pig. The foot (F) of the pig is toward the bottom and head (H) is toward the top of the image. The orientation is continuously updated during the video and shown in the box in the lower left. Size calibration is shown on the right axis. The right coronary (RC) and left anterior descending (LAD) are shown from their origins superior (cranial) to the aortic (A) valve. Contrast fills primarily arteries, the left ventricle (LV), and the left atrium (LA). Typical diameters of the RC and LAD of 3-4 mm and aorta 10-15 mm are apparent. The circumflex (CFX) coronary artery is largely obscured by the left atrium. In the lower half of the figure are the right and left internal mammary arteries (RIMA, LIMA, respectively), vena cava (VC), and descending thoracic aorta. As the image rotates in the video the right dominant feature of the pig coronary artery anatomy, similar to humans, is shown by the right coronary artery traversing the posterior aspect of the heart to perfuse the posterior myocardium.
National Institutes of Health (NIH)
- 10/13-10/18, NIH NCRR, "Indiana Clinical and Translational Sciences Institute", UL1 RR025761, Co-Investigator (Principal Investigator: A. Shekhar), 15% effort
- 4/1/12-3/31/17, NIH NHLBI, “TRPC channels in the metabolic syndrome”, R01 HL115140, Co-Investigator (Principal Investigator: A. Obukhov), 10% effort
- 4/1/13-3/31/18, NIH NHLBI, “Purinergic signaling in atherosclerosis”, R01 HL112883, Co-Investigator (Principal Investigator: C.I. Seye), 5% effort
- 1/1/15-12/31/16, IUPUI Graduate Student Research Imaging Fellowship, “Catheter-based photoacoustic imaging platform for real-time assessment of atherosclerosis”, Predoctoral Fellowship Mentor for A. Kole
- 1/1/15-12/31/16, American Heart Association, “Effect of SERCA dysfunction and ER/SR stress on coronary artery disease”, #15PRE25280001, Predoctoral Fellowship Mentor for S. Rodenbeck
- 6/1/15-5/31/20, NIH NIDDK, “Indiana diabetes research center”, P30 DK097512-01A1, Core Director, “Swine Core” (Principal Investigator: R. Mirmira), 5% effort
- 7/1/15-6/30/19, NIH NHLBI, “In vivo photoacoustic sensing of lipid laden plaque”, HL125385-01A1, Co-Investigator, subcontract from Purdue University, (Principal Investigator: J.-X. Cheng), 10% effort
Corporate and Private Foundation
- 7/8/15-9/30/16, Eli Lilly & Company, “Glargine insulin effects on fatty liver and cardiovascular disease", Principal Investigator, 7% effort.
- 10/04-ongoing, Purdue-Indiana University Comparative Medicine Center, "Ossabaw Swine Facility", Principal Investigator, 5% effort
- 10/1/13-3/31/16, IUSM Strategic Research Initiative (SRI) Center of Excellence in Cardiovascular Research (CECARE), “Imaging for early diagnosis of unstable plaque and vascular calcification”, Principal Investigator, 3% effort
- 7/15-7/17, NIH NCATS, Indiana Clinical and Translational Sciences Institute (CTSI) Collaboration in Biomedical/Translational Research (CBR/CTR) Pilot Program Grants UL1 TR001108, “A pig model of progressive chronic kidney disease”, Co-Investigator (Co-Principal Investigators: S. Moe and A.N. Baird), 0% effort