Bio

Honors & Awards


  • The American Physiological Society Renal Section Research Recognition, Experimental Biology 2017: American Physiology Society (April 22-26, 2017)

Boards, Advisory Committees, Professional Organizations


  • Editorial board, bio-protocol (2017 - Present)

Professional Education


  • Bachelor of Science, Jilin University (2007)
  • Doctor of Philosophy, Temple University (2012)

Stanford Advisors


Research & Scholarship

Current Research and Scholarly Interests


Diabetic nephropathy contributes 44% cases of the chronic kidney disease. By comparing the transcriptional profile of diabetic mice with/without kidney disease, I discovered that several inflammatory regulatory genes determine the disease progression, which can be used as therapeutic targets and diagnostic biomarkers.

For the 1st time, I discovered a method to break kidney glomeruli into single cells and quantify them by flow cytometry, which eliminates the need of cell counting under microscope and speeds up the experiment from weeks to 2 days. This technology was used to analyze leukocyte infiltration in mice, and can be used in other fields of glomerular study.

With a successful injection rate of 80-90%, I perform hydrodynamic injection (tail vein) to over-express protein in mice for at least 12 weeks and study its biological function in type I diabetes and anti-GBM mice model with macroalbuminuria.

V5 peptide is commonly used to label recombinant proteins, yet its small size prevents the detection by two different antibodies of a sandwich ELISA. For the 1st time, I developed an anti-V5 competitive ELISA method which uses only one antibody to quantify V5 tagged recombinant protein in cell lines and mice. This ELISA can be used to confirm over-expression of recombinant protein in cell lines and mice serum by its V5 tag.

Lab Affiliations


  • Vivek Bhalla, Department of Nephrology (2/15/2013 - 2/15/2015)

Teaching

Graduate and Fellowship Programs


  • Nephrology (Fellowship Program)

Publications

All Publications


  • Murine glomerular transcriptome links endothelial cell-specific molecule-1 deficiency with susceptibility to diabetic nephropathy. PloS one Zheng, X., Soroush, F., Long, J., Hall, E. T., Adishesha, P. K., Bhattacharya, S., Kiani, M. F., Bhalla, V. 2017; 12 (9): e0185250

    Abstract

    Diabetic nephropathy (DN) is the leading cause of kidney disease; however, there are no early biomarkers and no cure. Thus, there is a large unmet need to predict which individuals will develop nephropathy and to understand the molecular mechanisms that govern this susceptibility. We compared the glomerular transcriptome from mice with distinct susceptibilities to DN at four weeks after induction of diabetes, but before histologic injury, and identified differential regulation of genes that modulate inflammation. From these genes, we identified endothelial cell specific molecule-1 (Esm-1), as a glomerular-enriched determinant of resistance to DN. Glomerular Esm-1 mRNA and protein were lower in DN-susceptible, DBA/2, compared to DN-resistant, C57BL/6, mice. We demonstrated higher Esm-1 secretion from primary glomerular cultures of diabetic mice, and high glucose was sufficient to increase Esm-1 mRNA and protein secretion in both strains of mice. However, induction was significantly attenuated in DN-susceptible mice. Urine Esm-1 was also significantly higher only in DN-resistant mice. Moreover, using intravital microscopy and a biomimetic microfluidic assay, we showed that Esm-1 inhibited rolling and transmigration in a dose-dependent manner. For the first time we have uncovered glomerular-derived Esm-1 as a potential non-invasive biomarker of DN. Esm-1 inversely correlates with disease susceptibility and inhibits leukocyte infiltration, a critical factor in protecting the kidney from DN.

    View details for DOI 10.1371/journal.pone.0185250

    View details for PubMedID 28934365

  • Antidiabetic and Antinephritic Activities of Aqueous Extract of Cordyceps militaris Fruit Body in Diet-Streptozotocin-Induced Diabetic Sprague Dawley Rats OXIDATIVE MEDICINE AND CELLULAR LONGEVITY Liu, C., Song, J., Teng, M., Zheng, X., Li, X., Tian, Y., Pan, M., Li, Y., Lee, R. J., Wang, D. 2016

    Abstract

    Cordyceps militaris has long been used as a crude drug and folk tonic food in East Asia. The present study aims to evaluate the antidiabetic and antinephritic effects of the aqueous extract of the Cordyceps militaris fruit body (CM) in diet-streptozotocin- (STZ-) induced diabetic rats. During four weeks of continuous oral administration of CM at doses of 0.5, 1.0, and 2.0?g/kg and metformin at 100?mg/kg, the fasting blood glucose and bodyweight of each rat were monitored. Hypoglycemic effects of CM on diabetic rats were indicated by decreases in plasma glucose, food and water intake, and urine output. The hypolipidemic activity of CM was confirmed by the normalization of total cholesterol, triglycerides, and low- and high-density lipoprotein cholesterol in diabetic rats. Inhibitory effects on albuminuria, creatinine, urea nitrogen, and n-acetyl-?-d-glucosaminidase verified CM's renal protective activity in diabetic rats. Furthermore, CM exerted beneficial modulation of inflammatory factors and oxidative enzymes. Compared with untreated diabetic rats, CM decreased the expression of phosphor-AKT and phosphor-GSK-3? in the kidneys. Altogether, via attenuating oxidative stress, CM displayed antidiabetic and antinephritic activities in diet-STZ-induced diabetic rats.

    View details for DOI 10.1155/2016/9685257

    View details for Web of Science ID 000377409000001

    View details for PubMedID 27274781

    View details for PubMedCentralID PMC4870376

  • Study of the analgesic activities, chronic toxicity and addictive potential of Jia-Yuan-Qing pill in rats EXPERIMENTAL AND THERAPEUTIC MEDICINE Tian, Y., Teng, L., Wang, Z., Zhao, M., Meng, Q., Lu, J., Tian, J., Zhang, W., Zheng, X., Wang, D., Teng, L. 2015; 9 (6): 2349-2355
  • The missing link: studying the alternative TGF- pathway provides a unifying theory for different components of diabetic nephropathy. Diabetes Zheng, X., Bhalla, V. 2015; 64 (6): 1898-1900

    View details for DOI 10.2337/db15-0184

    View details for PubMedID 25999532

    View details for PubMedCentralID PMC4439567

  • G-protein coupled receptor-associated sorting protein 1 (GASP-1), a ubiquitous tumor marker EXPERIMENTAL AND MOLECULAR PATHOLOGY Zheng, X., Chang, F., Zhang, X., Rothman, V. L., Tuszynski, G. P. 2012; 93 (1): 111-115

    Abstract

    Using an innovative "2-D high performance liquid electrophoresis" (2-D HPLE) technology we identified that a specific fragment of G-protein coupled receptor-associated sorting protein 1 (GASP-1) was present in the sera of breast cancer patients and was over-expressed in early and late stage breast tumors (Tuszynski, G.P. et al., 2011). In this study we further investigated the significance of GASP-1 as a tumor marker by investigating the expression GASP-1 in different kinds of tumors as well as in the sera of patients with various cancers. Over expression of GASP-1 was detected in brain, pancreatic, and breast cancers as compared to their respective normal tissues as assessed by immunohistochemical staining of tissue arrays using a "peptide specific" GASP-1 antibody. We found that across these cancers, GASP-1 was expressed approximately 10 fold more in the cancer as compared to normal tissue. The increase in GASP-1 expression was also seen in hyperplastic and inflammatory lesions of breast and pancreatic cancers as compared to normal tissue. GASP-1 was primarily expressed in the tumor epithelium of the epithelial-derived cancers and in the transformed glial cells of the brain tumors. Using a sensitive "competitive ELISA" for GASP-1, we found that sera from patients with brain, liver, breast and lung cancers expressed 4-7 fold more GASP-1 peptide than sera from normal healthy individuals. These studies identify GASP-1 as a potential new serum and tumor biomarker for several cancers and suggest that GASP-1 may be a novel target for development of cancer therapeutics.

    View details for DOI 10.1016/j.yexmp.2012.03.013

    View details for Web of Science ID 000305924000015

    View details for PubMedID 22483848

  • G-protein coupled receptor-associated sorting protein 1 (GASP-1), a potential biomarker in breast cancer EXPERIMENTAL AND MOLECULAR PATHOLOGY Tuszynski, G. P., Rothman, V. L., Zheng, X., Gutu, M., Zhang, X., Chang, F. 2011; 91 (2): 608-613

    Abstract

    An innovative "2-D high performance liquid electrophoresis" (2-D HPLE) technology was used to identify serum biomarkers associated with the early stage of breast cancer in addition to other more advanced stages. 2-D HPLE is a newly developed electrophoretic technology that separates 100s of serum albumin complexes on a polyvinyl membrane based on their surface charges. Association of cancer proteins or their fragments (biomarkers) with pre-existing albumin complexes in the blood of cancer patients results in altered mobility on the membrane. Using 2-D HPLE we identified that a specific fragment of G-protein coupled receptor-associated sorting protein 1 (GASP-1) was present in the sera of patients with early stage disease but absent in sera of normal patients. GASP-1 has been shown to modulate lysosomal sorting and functional down-regulation of a variety of G-protein coupled receptors in neuronal cells. However, no reports have linked GASP-1 to breast cancer pathogenesis. GASP-1 was detected in tumor extracts of 7 cases of Stage 2 and Stage 3 breast cancers, but not in adjacent normal tissue as revealed by western blot analysis using an antibody developed against a GASP-1 peptide identified by our 2-D HPLE technology. Using this antibody, we immunohistochemically detected over-expression of GASP-1 in all of 107 cases of archived ductal breast carcinoma tumor samples, while normal adjacent breast tissue from 12 cases of ductal carcinoma showed little or no staining. Additionally, all 10 cases of metastatic breast carcinoma present in lymph nodes were positive. Strong positive GASP-1 staining was observed in all tumor tissue including ductal carcinoma in situ (DCIS) and invasive ductal carcinoma. Additionally, we observed a wide spectrum of enhanced staining of premalignant ductal epithelial cells present in benign ducts and those found in atypical ductal hyperplasia (ADH). These studies identify GASP-1 as a potential new serum and tumor biomarker for breast cancer and suggest that GASP-1 may be a novel target for the development of breast cancer therapeutics.

    View details for DOI 10.1016/j.yexmp.2011.06.015

    View details for Web of Science ID 000295907700018

    View details for PubMedID 21791203

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