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Michael Sturek, Ph.D.

Sturek_M_office_photo_v1c_exposureweb.jpg

Professor, Department Chair
Full Member, Indiana University Graduate Faculty

Department of Cellular & Integrative Physiology
Indiana University School of Medicine
635 Barnhill Drive, Room 385
Indianapolis, Indiana 46202-5120

Professor of Biomedical Engineering - Purdue BME
Purdue University
West Lafayette, Indiana 47907

E-mail: msturek@iu.edu
Phone: 317-274-7772
Facsimile: 317-274-3318


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
Research  (scroll down) Coworkers Publications

Research

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
research interests35bib.pdf


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). This designation makes internal funding available from the CTSI Core Pilot Funding Opportunity. The next deadline for applications is October 18, 2010. The guidelines and application are available at https://www.indianactsi.org/grants where Indiana CTSI members can access by logging in using their university username and password. Typically up to $10,000 in services can be requested.

Overview and Tour of Purdue Ossabaw Facility
Spencer, J. (Editor). Indiana University Home Pages. SPECIAL ISSUE The Life Sciences at IU. February 2009.
http://homepages.indiana.edu/web/page/normal/10111.html

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.
Overall Organization and Infrastructure v1.pdf

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 v6.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.
Ossabaw pig v5.pdf

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.
Typical design chronic studies v1.pdf

Tissues Available
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 Brandy Sparks for current pricing (sparks5@iupui.edu).

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 to initiate the MTA (malloosh@iupui.edu).

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 Brandy Sparks for current availability (sparks5@iupui.edu). 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.). (Standard Ossabaw initial contact letter v12.doc)

Availability of tissues and live swine will depend on continued extramural funding and demand from investigators.


Description of the Video Tour

Treadmill exercise.mpg
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.

Grant Funding

National Institutes of Health

  • UL1 RR025761, 10/13-10/18, “Indiana Clinical and Translational Sciences Institute”, Co-Investigator, 15% effort (Principal Investigator A. Shekhar)
  • DK084324, 7/09-7/15, “Mechanisms of glycemic improvement following gastrointestinal surgery”, Co-Investigator, 5% effort, (Principal Investigator D.R. Flum), subcontract from University of Washington, $294,641
  • HL062552, 4/10-4/15, “Exercise, diabetes, and coronary smooth muscle Ca2+”, Principal Investigator, 20% effort, $2,434,087
  • HL106792, 4/1/11-3/31/15, “Improved therapeutics for drug eluting stents”, Co-Investigator, 10% effort, (Principal Investigator: A. Panitch), subcontract from Purdue University, $248,451”
  • HL115140, 4/1/12-3/31/17, “TRPC channels in the metabolic syndrome”, Co-Investigator, 10% effort, (Principal Investigator: A. Obukhov)
  • HL112883, 4/1/13-3/31/18, “Purinergic signaling in atherosclerosis”, Co-Investigator, 10% effort, (Principal Investigator: C.I. Seye)
  • HL117990, 10/1/13-9/30/17, “Micro-mechanical role of hypertension in intimal hyperplasia”, Co-Investigator, 2% effort, (Principal Investigator: G. Kassab)
  • 13GHSU260, 11/1/13-10/31/14, “Progression of diabetic cystopathy in the Ossabaw pig using bladder monitor", DiaComp Pilot & Feasibility project, Co-Investigator, 0% effort, (Principal Investigator: C.R. Powell)

Internal

  • 10/04-ongoing, Purdue-Indiana University Comparative Medicine Center, “Ossabaw Swine Facility”, Principal Investigator, 5% effort, ~$75,000 annually
  • 10/1/13-9/30/15, 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, $116,606
  • 3/15/13-3/15/15, Indiana University Collaborative Research Grants (IUCRG), “Thrombopoietic agents agents in bone regeneration: development of a minipig bone healing model”, Co-Investigator, 0% effort, (Principal Investigator: M. Kacena)

Corporate and Private Foundation 

  • 9/1/13-8/31/14, The Cardiometabolic Disease Research Foundation, “Epicardial fat and coronary artery disease 2”, Principal Investigator, 5% effort, $301,415
Research (scroll up) Coworkers Publications

Updated: 09/23/2013