Department of Cellular and Structural Biology

CSB Faculty

 

James Donald Lechleiter, Ph.D.

Professor
Director of the Optical Imaging Core
Director STRF Neuroscience Program ad interim

 

University of Arizona, 1984

 

STRF, 207.2
(210) 562-4043
Lechleiter@uthscsa.edu

 

In general, Dr. Lechleiter's laboratory is interested in the molecular and cellular mechanisms of neuroprotection that occur in response to ischemic stress, acute brain injury and aging. Recent advances in their laboratory revealed how natural healing mechanisms could be activated by boosting mitochondrial energy (ATP) production in astrocytes, the major support cell in the brain. Their approach is substantially different from other neuroprotective strategies that have thus far proven unsuccessful. A strategy that increases energy production is inherently robust, since multiple protective processes benefit.

 

One specific area of research is an investigation of the underlying protective mechanisms mediated by stimulation of purinergic P2Y1 receptors, which are primarily expressed on astrocytes. A second major research project is an examination of the neuroprotective efficacy of thyroid hormones via stimulation of fatty acid oxidation (FAO), which appears to occur predominantly in astrocytes. A third area of research is focused on the long-term neurological consequences of repetitive traumatic brain injury (TBI). Finally, Dr. Lechleiter's laboratory is investigating the role of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in the development of age-associated neurological deficits.

 

Discovery leads to patent for novel method of treating traumatic brain injury
A researcher in the School of Medicine at The University of Texas Health Science Center at San Antonio, Professor James Lechleiter, received a U.S. patent (No. 8,618,074) Dec. 31 for his discovery that a class of compounds is protective against traumatic brain injury (TBI). The experimental test tissues pictured were obtained from a 60-year-old human patient who had undergone a temporal lobectomy to relieve epilepsy. Neurons are visible in red, astrocytes (caretaker cells) in green. The specimen on the right was placed in a solution containing 2-methylthio-ADP, one of a class of compounds called purinergic receptor ligands. The specimen on the left was placed in untreated solution. The specimens are shown five days after ischemic trauma that usually results in killing of neurons and astrocytes. 2-methylthio-ADP preserved many neurons and astrocytes in the treated specimen.

Dr. Lechleiter's Videos:
    Video Introduction to Dr. Lechleiter's Lab!

     

    Human Brain Tissue Movie

     

    Spiral Ca2+ waves in Xenopus oocyte Movie
    Intracellular Ca2+ is a ubiquitous second messenger that controls the activity of a multitude of enzymatic processes. Ca2+ cannot be metabolized in a manner that is analogous to the cycle of protein phosphorylation / de-phosphorylation. Rather, Ca2+ signals are mediated by changes in concentration of the ion. Studies in our laboratory revealed spiral waves of intracellular Ca2+ release induced by inositol 1,4,5 trisphosphate (IP3) (Figure 2). Spiral waves are the trademark pattern formations of excitable media and have been described in other systems such as the classic Belousov-Zhabotinsky chemical reaction, aggregating slime mold, and electrical activity in neuronal tissue. The active propagation of Ca2+ release in the form of Ca2+ waves provides an efficient mechanism to communicate hormonal signals over long distances.


Dr. Lechleiter lectures primarily to graduate students on biophysics, cell biology and neurobiology as well as the fundamental principles of light microscopy. Since 2009, he has lectured in "Fundamentals in Biomedical Sciences" (INTD 5000), which is the core course for all incoming IMGP / IBMS graduate students. He developed the curriculum for the Imaging Week module and was a lecturer on ER Stress in the Obesity Week module. He currently directs "Practical Optical Microscopy" (CSBL 5083), which is widely attended by not only students, but by faculty and staff. He also continues to lecture in multiple courses that are generally offered on an annual basis including Biology of Aging (CSBL 6048), Molecular, Cellular and Developmental Neuroscience (INTD 5040), Advanced Cell and Molecular Biology (INTD 5007), Methods in Cell Biology Course (CSBL 5007), Cell Signaling Mechanisms (INTD 6033) and Advanced Molecular Cell Biology (MMED 6016). As can be discerned by the course numbers, these lectures were given in multiple departments and programs. Finally, the Henry Stewarts talks online (www.hstalks.com) created a video of his lecture "Impact of mitochondria on astrocyte neuroprotection in video series entitled: "The Physiology and Pathophysiology of Neuroglia".

 

He has also provided research training and mentoring at the high school, undergraduate, graduate, post-doctoral and research assistant professor levels. Overall, he has directed 2 MS thesis, 10 Ph.D. dissertations (4 are active, 2 URMs) and 10 post-doctoral fellows. Moreover, he has supervised 33 rotation graduate students, 10 undergraduate students and 7 high school students. He has been a member of the supervising committees of over 50 Ph.D. dissertations and 11 Master's theses.

Recent Publications:
Tiwari M, Sharma LK, Vanegas D, Callaway DA, Bai Y, Lechleiter JD, Herman B. A nonapoptotic role for CASP2/caspase 2: modulation of autophagy. Autophagy. 2014 Jun;10(6):1054-70.

 

Zheng W, Talley Watts L, Holstein DM, Wewer J, Lechleiter JD. P2Y1R-initiated, IP3R-dependent stimulation of astrocyte mitochondrial metabolism reduces and partially reverses ischemic neuronal damage in mouse. J Cereb Blood Flow Metab. 2013 Apr;33(4):600-11.

 

Talley Watts L, Sprague S, Zheng W, Garling RJ, Jimenez D, Digicaylioglu M, Lechleiter JD. Purinergic 2Y1 receptor stimulation decreases cerebral edema and reactive gliosis in a traumatic brain injury model. J Neurotrauma. 2013 Jan 1;30(1):55-66.

 

Chocron ES, Sayre NL, Holstein D, Saelim N, Ibdah JA, Dong LQ, Zhu X, Cheng SY, Lechleiter JD. The trifunctional protein mediates thyroid hormone receptor-dependent stimulation of mitochondria metabolism. Mol Endocrinol. 2012 Jul;26(7):1117-28.

 

Zheng W, Watts LT, Holstein DM, Prajapati SI, Keller C, Grass EH, Walter CA, Lechleiter JD. Purinergic receptor stimulation reduces cytotoxic edema and brain infarcts in mouse induced by photothrombosis by energizing glial mitochondria. PLoS One. 2010 Dec 22;5(12):e14401.

 

Representative Publications:
Bollo M, Paredes RM, Holstein D, Zheleznova N, Camacho P, Lechleiter JD. Calcineurin interacts with PERK and dephosphorylates calnexin to relieve ER stress in mammals and frogs. PLoS One. 2010 Aug 5;5(8):e11925.

 

Saelim N, Holstein D, Chocron ES, Camacho P, Lechleiter JD. Inhibition of apoptotic potency by ligand stimulated thyroid hormone receptors located in mitochondria. Apoptosis. 2007 Oct;12(10):1781-94.

 

Wu J, Holstein JD, Upadhyay G, Lin DT, Conway S, Muller E, Lechleiter JD. Purinergic receptor-stimulated IP3-mediated Ca2+ release enhances neuroprotection by increasing astrocyte mitochondrial metabolism during aging. J Neurosci. 2007 Jun 13;27(24):6510-20.

Dr. Lechleiter's Lab:
    Ramaswarmy Sharma, Ph.D., Research Assistant Professor,
    Caspase 2, Apoptosis, Differentiation and Bone growth.

     

    Deborah Holstein, Senior Laboratory Technician.
    High-throughput Screening of Neuroprotective Molecules.

Postdoctoral fellows:
    Naomi Sayre, Ph.D. Postdoctoral fellow,
    Thyroid Hormone Regulation of Glial Mitochondrial Metabolism and Neuroprotection.
Graduate students:
    Yanan Chen, Biology of Aging PhD student,
    The protective role of Calcineurin Abeta in ER stress via activation of the Unfolded Protein Responses (UPR) in astrocytes.

     

    Wenrui Ye, Neuroscience PhD student,
    Impact Of Prenatal Nutrition On Brain Development And Life-Long Behavior.

     

    Elizabeth Fisher, Genetics, Genomics and Development PhD student,
    Glutamate metabolism and Astrocyte mediated Neuroprotection.

     

    Brian Joseph Stoveken, Biology of Aging PhD student,
    ER Stress and age-associated neurological deficits.

     

    Mikaela Sifuentes, Neuroscience PhD student,
    Mitochondrial Trifunctional Protein (MTP) and Respiratory complexes using Super-resolution.