6529-Territo, Paul
Faculty

Paul R. Territo, PhD, MS

Professor of Medicine

Address
BRTC 214
CPHR
IN
Indianapolis, IN

Bio

Paul R. Territo received his Masters in Cardio-Renal Physiology from California Polytechnic Univrsity in 1993, and his Ph.D. from UNLV in 1996 in Cardiovascular and Respiratory Physiology. During his postdoctoral fellowship at the Laboratory of Cardiac Energetics at the NIH’s National Heart, Lung, and Blood Institute, he obtained critical training in noninvasive imaging technology and biophysics, which included Positron Emission Tomography (PET), Computed Tomography (CT), and Magnetic Resonance Imaging (MRI). From that time forward, he has focused his research on the development and application of imaging technologies to study disease progression, and evaluate the role of novel therapeutics on physiological processes. Leveraging these experiences, from 2001 to 2008, Dr. Territo as part of Eli Lilly’s drug discovery team developed novel imaging based biomarkers for therapeutic development, and rose to the rank of Senior Scientist. Shortly thereafter, Dr. Territo joined the faculty of Indiana University School of Medicine as an Associate Professor of Research in the Department of Radiology and Imaging Sciences, where served as the Director of the Preclinical Imaging Core. Over this interval, Dr. Territo continued to develop novel imaging based biomarkers for both preclinical and clinical assessment. In 2021, Dr. Territo was promoted to Professor of Medicine, where his lab continues to develops state-of-the-art biomarkers for monitoring disease progression and therapeutic response for Alzheimer’s Disease and Related Dementia (ADRD), oncology, and cardiovascular diseases. Currently, Dr. Territo serves as the Scientific Director of the IU Simon Cancer Signature Center Imaging Center.

Key Publications

1.    My early work focused on the biophysics and bioenergetics of metabolic control in heart disease. This work focused on demonstrating the role of Ca2+ as a second messenger of metabolic signaling in normal and diseased hearts. This early work focused on isolated mitochondria and the control networks that coordinate oxidative phosphorylation substrate flux, and demonstrated for the first time that the F0/F1-ATPase was Ca2+ sensitive and when combined with the known effects Ca2+ on NADH production via the TCA cycle, could explain the tight coupling of energy demand by the sarcomere and ATP production by the mitochondria. This work further demonstrated that this coupling was dose dependent, very rapid, and was tightly linked to SR release of Ca2+. This body of work has helped to redefine the role of Ca2+ in energy production in normal and diseased myocardium, and has served as a platform for investigation of novel cardiac drugs in heart disease. In the body of work below, I have served as the primary or senior author in all of these studies. 

a.    Balaban, RS, S. Bose, S. A. French, and P.R. Territo  (2003) “Role of calcium in metabolic signaling between cardiac sarcoplasmic reticulum and mitochondria in vitro.” Am J Physiol Cell Physiol. 284(2):C285-93.
 
b.    P.R. Territo, S. A. French, and R.S. Balaban. (2001)  Simulation of cardiac work transitions, in vitro: effects of simultaneous Ca2+ and ATPase additions on isolated porcine heart mitochondria. Cell Calcium. 30(1):19-27.
 
c.     P.R. Territo, S.A. French, M.C. Dunleavy, F.J. Evans, and R.S. Balaban (2001) “Calcium activation of oxidative phosphorylation: Rapid kinetics of mVO2, NADH and Light Scattering” J. Biol. Chem. 276: 2586-2599
 
d.    P.R. Territo, V.K. Mootha, S.A. French, and R.S. Balaban (2000) “Activation of heart mitochondrial oxidative phosphorylation: Role of the Fo/F1ATPase.” Am. J. Physiol. 278: C423-C435.

2.    A key area of focus in my career has been the development of technologies that permit determination of physiological or pharmacological function. The bulk of this work has focused on optical, magnetic resonance imaging, and positron emission tomography (PET) ligand development, and have enabled our teams to non-invasively probe neurological and cardiovascular function with time. In the body of work below, I have served as the primary, co-investigator, or senior author in all of these studies. 

a.    T. Tirkes, CY Jeon, L Li, AY Joon, TA Seltman, M Sankar, SA Persohn, and P.R. Territo. Association of Pancreatic Steatosis With Chronic Pancreatitis, Obesity, and Type 2 Diabetes Mellitus. Pancreas. 2019 Mar;48(3):420-426.

b.    P.R. Territo, Riley AA, McCarthy BP, and Hutchins GD. Measurement of cardiovascular function using a novel view-sharing PET reconstruction method and tracer kinetic analysis. EJNMMI Phys. 2016 Dec;3(1):24.

c.     P.R. Territo, Meyer JA, Peters JS, Riley AA, McCarthy BP, Gao M, Wang M, Green MA, Zheng QH, and Hutchins GD. Characterization of 11C-GSK1482160 for Targeting the P2X7 Receptor as a Biomarker for Neuroinflammation. J Nucl Med. 2017 Mar;58(3):458-465.

d.    K.K. Yoder, G.D. Hutchins, B.H. Mock, X. Fei, W.L. Winkle, B.D. Gitter, P.R. Territo, and Q.H. Zheng (2009) “Dopamine transporter binding in rat striatum:  A comparison of O-methyl and N-methyl [11C]b-CFT”, Nuc. Med. Biol. Jan;36(1):11-6.

3.    The development of imaging based biomarkers for in vivo testing novel therapeutics in appropriate and validated model systems are key aspects of translating model based mechanistic work to clinical applications. Our lab has focused on development of validated imaging methods in animal models, and formulating a framework for quantification of the biomarker of interest utilizing murine bioluminescence (BLI) and/or 18F-FDG PET as a marker of tumor cell growth and development. Although methods such as BLI are not directly translational, the knowledge gained through this work provides a rapid and inexpensive method to evaluate novel therapeutic regimes non-invasively, and are often followed by bridging work to more expensive clinically relevant modalities such as CT, MRI, and PET. This approach in our institution has become the preferred route for novel therapeutics testing in oncology studies. In the body of work below, I serve as the lead investigator, senior investigator or co-investigator in all of these studies.

a.    P.R. Territo, Maluccio M, Riley AA, McCarthy BP, Fletcher J, Tann M, Saxena R, Skill NJ. Evaluation of 11C-acetate and 18F-FDG PET/CT in mouse multidrug resistance gene-2 deficient mouse model of hepatocellular carcinoma. BMC Med Imaging. 2015 May 16;15:15. doi: 10.1186/s12880-015-0058-z. PMID: 25981587; PMCID: PMC4493966.
 
b.    H.E. Shannon, M.L. Fishel, J. Xie, D. Gu, B.P. McCarthy, A.A. Riley, A.L. Sinn, J.M. Silver, K. Peterman, M.R. Kelley, H. Hanenberg, M. Korc, K. E. Pollok, and P.R. Territo (2015) “Longitudinal Bioluminescence Imaging of Primary versus Abdominal Metastatic Tumor Growth in Orthotopic Pancreatic Tumor Models in NSG Mice”, Panc Jan;44(1):64-75
 
c.     T.W. Corson, B.C. Samuels, A.A. Wenzel, A.J. Geary, A.A. Riley, B.P. McCarthy, H. Hanenberg, B.J. Bailey, P.I. Rogers, K.E. Pollok, G. Rajashekhar, and P.R. Territo (2014) “Multimodality Imaging Methods for Assessing Retinoblastoma Orthotopic Xenograft Growth and Development” PLoS One, Jun 5;9(6)
 
d.    J.R. Gehlhausen, S.J. Park, A.E. Hickox, M. Shew, K. Staser, S.D. Rhodes, K. Menon, J.D. Lajiness, M. Mwanthi, X. Yang, J. Yuan, P.R. Territo, G. Hutchins, G. Nalepa, F.C. Yang, S.J. Conway, M.G. Heinz, A. Stemmer-Rachamimov, C.W. Yates, D. Wade Clapp. (2015) “A murine model of neurofibromatosis type 2 that accurately phenocopies human schwannoma formation.” Hum Mol Genet. Jan;24(1),1-8

4.    In addition to the above listed contributions, and in collaboration with a number of investigators at IU, I have developed several model systems for the testing of novel therapeutics and/or systems. This work has focused on the formation of well characterized canine models of disease (i.e. osteoporosis, seizure), and then developed rigorous system from which to evaluate the therapeutic of interest. In virtually all cases, this paradigm has been the basis for drug candidate selection. In each of these papers, I have served as the primary investigator or co-investigator.  

a.    Allen MR, P.R. Territo, C Lin, S Persohn, L Jiang, AA Riley, BP McCarthy, CL Newman, DB Burr, GD Hutchins. (2015). “In vivo UTE-MRI Reveals Positive Effects of Raloxifene on Skeletal Bound Water in Skeletally Mature Beagle Dogs.” J Bone Miner Res. 2015 Jan 31. [Epub ahead of print]
 
b.    P.R. Territo, H.E. Shannon, K. Newhall, S.D. Barnhart, S.C. Peters, D.R. Engleking, T. Bin, T.J. Burnett, J.M. Rodewald, B. Abdul-Karim, K.J. Freise. “Nonlinear Mixed Effects Pharmacokinetic/Pharmacodynamic Analysis of the Anticonvulsant Ameltolide (LY201116) In A Canine Seizure Model.” J Vet Pharmacol Ther. (2008) Dec;31(6):562-70.
 
c.     P.R. Territo, K.J. Freise, K. Newhall, S.D. Barnhart, S.C. Peters, D.R. Engleking, T.J. Burnett, B. Abdul-Karim, H.E. Shannon. (2007) “Development and Validation of the Maximal Electro-Shock Seizure Model in Dogs” J Vet Pharmacol Ther. Dec;30(6):508-15.

Titles & Appointments

  • Professor of Medicine
  • Education
    1996 PhD University of Nevada, Las Vegas
    1993 MS California Polytechnic State University
    1991 BS California Polytechnic State University
  • Research

    As an independent investigator working at the cross-roads of medicine and medical imaging, my research encompasses the assessment of disease progression and therapeutic response, where we leverage the expertise of our teams in Tracer Development and Validation, Pre-Clinical Imaging, and Medical Image Analysis. A key component of this translational research is the ability to develop novel imaging based biomarker approaches, provide validation of the methodologies, and then use these to serve as a springboard for mechanistic studies and/or therapeutic testing.  This research Positron Emission Tomography (PET), Computed Tomography (CT), and Magnetic Resonance Imaging (MRI) methods which map directly to clinical endpoints, and confirms these via autoradiography, immunohistology, and transcriptomics analyses to answer key questions about the mechanism of disease progression, and efficacy of novel therapeutics. This strategy has been extensively leveraged in the MODEL-AD U54 grant, where my lab serves as the deep phenotyping core and preclinical drug testing core in models of Late Onset Alzheimer’s Disease (LOAD). In addition, our lab is tightly integrated into the TREAT-AD U54 grant, where my lab provides preclinical testing in LOAD models for novel drugs and targets of LOAD. In addition, to these efforts, our lab is extensively exploring the underlying mechanisms which triggers the onset of LOAD, and by leveraging the aforementioned translational methods to study the drivers of neuroinflammation, and then develop therapeutic strategies for treating AD and related dementias.  

  • Publications
    Effects of renal sympathetic denervation on the stellate ganglion and the brain stem in dogs.
    Tsai WC; Chan YH; Chinda K; Chen Z; Patel J; Shen C; Zhao Y; Jiang Z; Yuan Y; Ye M; Chen LS; Riley AA; Persohn SA; Territo PR; Everett TH 4th; Lin SF; Vinters HV; Fishbein MC; Chen PS; Heart rhythm : the official journal of the Heart Rhythm Society 2016 Oct 5
    Characterization Of [11C]-GSK1482160 For Targeting The P2X7 Receptor As A Biomarker For Neuroinflammation.
    Territo PR; Meyer JA; Peters JS; Riley AA; McCarthy BP; Gao M; Wang M; Green MA; Zheng QH; Hutchins GD; Journal of nuclear medicine : official publication, Society of Nuclear Medicine 2016 Oct 20
    Novel application of complimentary imaging techniques to examine in vivo glucose metabolism in the kidney.
    Hato T; Friedman AN; Mang HE; Plotkin Z; Dube S; Hutchins GD; Territo PR; McCarthy BP; Riley AA; Pichumani K; Malloy CR; Harris RA; Dagher PC; Sutton TA; American journal of physiology. Renal physiology 2016 Jan 13
  • Professional Organizations
    International Society to Advance Alzheimer's Research and Treatment (ISTAART)
    Society for Neuroscience (SfN)
    Society for Nuclear Medicine and Molecular Imaging (SNMMI)
    World Molecular Imaging Society (WMIS)
  • Awards
    Org: National Institutes of Health
    Desc: Intramural Research Training Fellowship
    Scope: National
    Date: 1996-10-01

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