Bio

Professional Education


  • MD, Yale School of Medicine, Medicine (2015)
  • MHS, Yale School of Medicine, Medicine (2015)
  • BA, Johns Hopkins University, Biophysics (2010)

Publications

All Publications


  • Comparison of QT Interval Measurement Methods and Correction Formulas in Atrial Fibrillation AMERICAN JOURNAL OF CARDIOLOGY Tooley, J., Ouyang, D., Hadley, D., Turakhia, M., Wang, P., Ashley, E., Froelicher, V., Perez, M. 2019; 123 (11): 1822?27
  • Frequency and timing of short-term complications following abdominoperineal resection. The Journal of surgical research Tooley, J. E., Sceats, L. A., Bohl, D. D., Read, B., Kin, C. 2018; 231: 69?76

    Abstract

    Abdominoperineal resection (APR) is primarily used for rectal cancer and is associated with a high rate of complications. Though the majority of APRs are performed as open procedures, laparoscopic APRs have become more popular. The differences in short-term complications between open and laparoscopic APR are poorly characterized.We conducted a retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program database to determine the frequency and timing of onset of 30-d postoperative complications after APR and identify differences between open and laparoscopic APR.A total of 7681 patients undergoing laparoscopic or open APR between 2011 and 2015 were identified. The total complication rate for APR was high (45.4%). APRs were commonly complicated by blood transfusion (20.1%), surgical site infection (19.3%), and readmission (12.3%). Laparoscopic APR was associated with a 14% lower total complication rate compared to open APR (36.0% versus 50.1%, P<0.001). This was primarily driven by a decreased rate of transfusion (10.7% versus 24.9%, P<0.001) and surgical site infection (15.5% versus 21.2%, P<0.001). Laparoscopic APR had shorter length of stay and decreased reoperation rate but similar rates of readmission and death. Cardiopulmonary complications occurred earlier in the postoperative period after APR, whereas infectious complications occurred later.Short-term complications following APR are common and occur more frequently in patients who undergo open APR. This, along with factors such as risk of positive pathologic margins, surgeon skill set, and patient characteristics, should contribute to the decision-making process when planning rectal cancer surgery.

    View details for PubMedID 30278971

  • Perioperative outcomes of coronary artery bypass graft in renal transplant recipients in the United States: results from the Nationwide Inpatient Sample. Clinical transplantation Tooley, J. E., Bohl, D. D., Kulkarni, S., Rodriguez-Davalos, M. I., Mangi, A., Mulligan, D. C., Yoo, P. S. 2016; 30 (10): 1258-1263

    Abstract

    Cardiovascular disease is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). In fact, death from cardiovascular disease is the number one cause of graft loss in kidney transplant (KTx) patients. Compared to patients on dialysis, CKD patients with KTx have increased quality and length of life. It is not known, however, whether outcomes of coronary artery bypass graft (CABG) surgery differ between CKD patients with KTx or on dialysis.This was a retrospective cohort study comparing CKD patients with KTx or on dialysis undergoing CABG surgery included in the Nationwide Inpatient Sample from 2002 to 2011. Logistic and linear regression models were used to estimate the adjusted associations of KTx on all-cause in-hospital mortality, length of stay, cost of hospitalization, and rate of complications in CABG surgery.CKD patients with KTx had decreased all-cause in-hospital mortality (2.68% vs 5.86%, odds ratio (OR)=0.56, 95% confidence interval (CI)=0.32 to 0.99, P=.046), length of stay (?=-2.96, 95% CI=-3.67 to -2.46, P<.001), and total hospital charges (difference=-$38884, 95% CI=-$48173 to -29596, P<.001). They also had decreased rate of a number of perioperative complications.CKD patient with KTx have better perioperative outcomes in CABG surgery compared to patients on dialysis.

    View details for DOI 10.1111/ctr.12816

    View details for PubMedID 27440000

  • Partners in Crime: Kidney Transplantation and Seizure Disorder. Transplantation proceedings Li, N., Jean, R., Tooley, J. E., Mulligan, D. C., Yoo, P. S. 2016; 48 (8): 2700-2708

    Abstract

    Seizure disorder is a common neurologic complication of kidney transplantation and often presents as a complex management challenge. Little is known about the risks mutually conferred by the 2 clinical entities and the effects of such risks on clinical outcomes. Using the National Inpatient Sample, our goal was to examine the effects of kidney transplantation and seizure disorder on mortality, hospitalization statistics, clinical complications, and cost of care. A history of kidney transplantation was shown to negatively affect the care of seizure disorder, and a history of seizure disorder also negatively affected the clinical outcomes of kidney transplantation. Our findings are important for initiating discussions and prompting future studies to further examine disease-specific risks of kidney transplantation.

    View details for DOI 10.1016/j.transproceed.2016.06.041

    View details for PubMedID 27788804

  • Changes in T-cell subsets identify responders to FcR-nonbinding anti-CD3 mAb (teplizumab) in patients with type 1 diabetes EUROPEAN JOURNAL OF IMMUNOLOGY Tooley, J. E., Vudattu, N., Choi, J., Cotsapas, C., Devine, L., Raddassi, K., Ehlers, M. R., McNamara, J. G., Harris, K. M., Kanaparthi, S., Phippard, D., Herold, K. C. 2016; 46 (1): 230-241

    Abstract

    The mechanisms whereby immune therapies affect progression of type 1 diabetes (T1D) are not well understood. Teplizumab, an FcR nonbinding anti-CD3 mAb, has shown efficacy in multiple randomized clinical trials. We previously reported an increase in the frequency of circulating CD8(+) central memory (CD8CM) T cells in clinical responders, but the generalizability of this finding and the molecular effects of teplizumab on these T cells have not been evaluated. We analyzed data from two randomized clinical studies of teplizumab in patients with new- and recent-onset T1D. At the conclusion of therapy, clinical responders showed a significant reduction in circulating CD4(+) effector memory T cells. Afterward, there was an increase in the frequency and absolute number of CD8CM T cells. In vitro, teplizumab expanded CD8CM T cells by proliferation and conversion of non-CM T cells. Nanostring analysis of gene expression of CD8CM T cells from responders and nonresponders versus placebo-treated control subjects identified decreases in expression of genes associated with immune activation and increases in expression of genes associated with T-cell differentiation and regulation. We conclude that CD8CM T cells with decreased activation and regulatory gene expression are associated with clinical responses to teplizumab in patients with T1D.

    View details for DOI 10.1002/eji.201545708

    View details for Web of Science ID 000368234800026

    View details for PubMedID 26518356

    View details for PubMedCentralID PMC4882099

  • Biomarkers in type 1 diabetes: application to the clinical trial setting CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY Tooley, J. E., Herold, K. C. 2014; 21 (4): 287-292

    Abstract

    Biomarkers of type 1 diabetes (T1D) are important for assessing risk of developing disease, monitoring disease progression, and determining responses to clinical treatments. Here we review recent advances in the development of biomarkers of T1D with a focus on their utility in clinical trials.Measurements of autoantibodies and metabolic outcomes have been the foundation of monitoring T1D for the past 20 years. Recent advancements have led to improvements in T-cell-specific assays that have been used in large-scale clinical trials to measure antigen-specific T cell responses. Additionally, new tools are being developed for the measurement of ? cell mass and death that will allow for more direct measurement of disease activity. Lastly, recent studies have used both immunologic and nonimmunologic biomarkers to identify responders to treatments in clinical trials.Use of biomarkers in the study of T1D has largely not changed over the past 20 years; however, recent advancements in the field are establishing new techniques that allow for more precise monitoring of disease progression. These new tools will ultimately lead to an improvement in understanding of disease and will be utilized in clinical trials.

    View details for DOI 10.1097/MED.0000000000000076

    View details for Web of Science ID 000338130600006

    View details for PubMedID 24937037

  • New and future immunomodulatory therapy in type 1 diabetes TRENDS IN MOLECULAR MEDICINE Tooley, J. E., Waldron-Lynch, F., Herold, K. C. 2012; 18 (3): 173-181

    Abstract

    Type 1 diabetes is a common autoimmune disease that affects millions of people worldwide and has an incidence that is increasing at a striking rate, especially in young children. It results from the targeted self-destruction of the insulin-secreting ? cells of the pancreas and requires lifelong insulin treatment. The effects of chronic hyperglycemia - the result of insulin deficiency - include secondary endorgan complications. Over the past two decades our increased understanding of the pathogenesis of this disease has led to the development of new immunomodulatory treatments. None have yet received regulatory approval, but this report highlights recent progress in this area.

    View details for DOI 10.1016/j.molmed.2012.01.001

    View details for Web of Science ID 000302455400006

    View details for PubMedID 22342807

  • Teplizumab Induces Human Gut-Tropic Regulatory Cells in Humanized Mice and Patients SCIENCE TRANSLATIONAL MEDICINE Waldron-Lynch, F., Henegariu, O., Deng, S., Preston-Hurlburt, P., Tooley, J., Flavell, R., Herold, K. C. 2012; 4 (118)

    Abstract

    The development and optimization of immune therapies in patients has been hampered by the lack of preclinical models in which their effects on human immune cells can be studied. As a result, observations that have been made in preclinical studies have suggested mechanisms of drug action in murine models that have not been confirmed in clinical studies. Here, we used a humanized mouse reconstituted with human hematopoietic stem cells to study the mechanism of action of teplizumab, an Fc receptor nonbinding humanized monoclonal antibody to CD3 being tested in clinical trials for the treatment of patients with type 1 diabetes mellitus. In this model, human gut-tropic CCR6(+) T cells exited the circulation and secondary lymph organs and migrated to the small intestine. These cells then produced interleukin-10 (IL-10), a regulatory cytokine, in quantities that could be detected in the peripheral circulation. Blocking T cell migration to the small intestine with natalizumab, which prevents cellular adhesion by inhibiting ?(4) integrin binding, abolished the treatment effects of teplizumab. Moreover, IL-10 expression by CD4(+)CD25(high)CCR6(+)FoxP3 cells returning to the peripheral circulation was increased in patients with type 1 diabetes treated with teplizumab. These findings demonstrate that humanized mice may be used to identify novel immunologic mechanisms that occur in patients treated with immunomodulators.

    View details for Web of Science ID 000299539500008

    View details for PubMedID 22277969

  • The 1.75 angstrom resolution structure of fission protein Fis1 from Saccharomyces cerevisiae reveals elusive interactions of the autoinhibitory domain ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS Tooley, J. E., Khangulov, V., Lees, J. P., Schlessman, J. L., Bewley, M. C., Heroux, A., Bosch, J., Hill, R. B. 2011; 67: 1310-1315

    Abstract

    Fis1 mediates mitochondrial and peroxisomal fission. It is tail-anchored to these organelles by a transmembrane domain, exposing a soluble cytoplasmic domain. Previous studies suggested that Fis1 is autoinhibited by its N-terminal region. Here, a 1.75 resolution crystal structure of the Fis1 cytoplasmic domain from Saccharomyces cerevisiae is reported which adopts a tetratricopeptide-repeat fold. It is observed that this fold creates a concave surface important for fission, but is sterically occluded by its N-terminal region. Thus, this structure provides a physical basis for autoinhibition and allows a detailed examination of the interactions that stabilize the inhibited state of this molecule.

    View details for DOI 10.1107/S1744309111029368

    View details for Web of Science ID 000296793300001

    View details for PubMedID 22102223

    View details for PubMedCentralID PMC3212442

  • Epidermal growth factor inhibits intestinal NHE8 expression via reducing its basal transcription AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY Xu, H., Zhang, B., Li, J., Chen, H., Tooley, J., Ghishan, F. K. 2010; 299 (1): C51-C57

    Abstract

    Sodium/hydrogen exchangers (NHEs) play a major role in Na(+) absorption, cell volume regulation, and intracellular pH regulation. Of the nine identified mammalian NHEs, three (NHE2, NHE3, and NHE8) are localized on the apical membrane of epithelial cells in the small intestine and the kidney. Although the regulation of NHE2 and NHE3 expression has been extensively studied in the past decade, little is known about the regulation of NHE8 gene expression under physiological conditions. The current studies were performed to explore the role of epidermal growth factor (EGF) on NHE8 expression during intestinal maturation. Brush-border membrane vesicles (BBMV) were isolated from intestinal epithelia, and Western blot analysis was performed to determine NHE8 protein expression of sucking male rats treated with EGF. Real-time PCR was used to quantitate NHE8 mRNA expression in rats and Caco-2 cells. Human NHE8 promoter activity was characterized through transfection of Caco-2 cells. Gel mobility shift assays (GMSAs) were used to identify the promoter sequences and the transcriptional factors involved in EGF-mediated regulation. Our results showed that intestinal NHE8 mRNA expression was decreased in EGF-treated rats and Caco-2 cells, and NHE8 protein abundance was also decreased in EGF-treated rats. The activity of the human NHE8 gene promoter transfected in Caco-2 cells was also reduced by EGF treatment. This could be explained by reduced binding of transcription factor Sp3 on the NHE8 basal promoter region in the presence of EGF. Pretreatment with MEK1/2 inhibitor UO-126 could prevent EGF-mediated inhibition of NHE8 gene expression. In conclusion, this study showed that EGF inhibits NHE8 gene expression through reducing its basal transcription, suggesting an important role of EGF in regulating NHE expression during intestinal maturation.

    View details for DOI 10.1152/ajpcell.00081.2010

    View details for Web of Science ID 000278887800008

    View details for PubMedID 20375273

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