Kavitha Yaddanapudi

Interests

Research

Cardiac Sarcoidosis, PET CT and PET MRI imaging of Sarcoidosis and Interstitial lung disease

Courses

Scholarly Contributions

Journals/Publications

• Bhattacharji, P., Moore, W., & Yaddanapudi, K. (2020). Keratin 17 is an imaging biomarker in lung cancers. Journal of thoracic disease, 12(9), 5062-5066.
  More info

  Computed tomographic (CT) features have demonstrated their value in classifying and assessing pulmonary nodules. Additionally, recent studies have shown the presence of keratin 17 (K17) in lung cancer is associated with increased mortality compared to patients with low/no K17 expression. The purpose of this study is to determine if there are CT imaging features that correlate with overexpression of K17 in patients with lung cancer.
• Thompson, C. M., Yanof, J. H., Wiegert, J., Bullen, J., Obuchowski, N., Yaddanapudi, K., & Halliburton, S. S. (2020). A pilot study of patient-specific cardiovascular MDCT dose maps and their utility in estimating patient-specific organ and effective doses in obese patients. Journal of cardiovascular computed tomography, 10(3), 265-8.
  More info

  Estimates of effective dose (E) for cardiovascular CT are obtained from a scanner-provided dose metric, the dose-length product (DLP), and a conversion factor. These estimates may not adequately represent the risk of a specific scan to obese adults.
• Brock, S. E., Rendon, B. E., Xin, D., Yaddanapudi, K., & Mitchell, R. A. (2014). MIF family members cooperatively inhibit p53 expression and activity. PloS one, 9(6), e99795.
  More info

  The tumor suppressor p53 is induced by genotoxic stress in both normal and transformed cells and serves to transcriptionally coordinate cell cycle checkpoint control and programmed cell death responses. Macrophage migration inhibitory factor (MIF) is an autocrine and paracrine acting cytokine/growth factor that promotes lung adenocarcinoma cell motility, anchorage-independence and neo-angiogenic potential. Several recent studies indicate that the only known homolog of MIF, D-dopachrome tautomerase (D-DT - also referred to as MIF-2), has functionally redundant activities with MIF and cooperatively promotes MIF-dependent pro-tumorigenic phenotypes. We now report that MIF and D-DT synergistically inhibit steady state p53 phosphorylation, stabilization and transcriptional activity in human lung adenocarcinoma cell lines. The combined loss of MIF and D-DT by siRNA leads to dramatically reduced cell cycle progression, anchorage independence, focus formation and increased programmed cell death when compared to individual loss of MIF or D-DT. Importantly, p53 mutant and p53 null lung adenocarcinoma cell lines were only nominally rescued from the cell growth effects of MIF/D-DT combined deficiency suggesting only a minor role for p53 in these transformed cell growth phenotypes. Finally, increased p53 activation was found to be independent of aberrantly activated AMP-activated protein kinase (AMPK) that occurs in response to MIF/D-DT-deficiency but is dependent on reactive oxygen species (ROS) that mediate aberrant AMPK activation in these cells. Combined, these findings suggest that both p53 wildtype and mutant human lung adenocarcinoma tumors rely on MIF family members for maximal cell growth and survival.
• Mitchell, R. A., & Yaddanapudi, K. (2014). Stromal-dependent tumor promotion by MIF family members. Cellular signalling, 26(12), 2969-78.
  More info

  Solid tumors are composed of a heterogeneous population of cells that interact with each other and with soluble and insoluble factors that, when combined, strongly influence the relative proliferation, differentiation, motility, matrix remodeling, metabolism and microvessel density of malignant lesions. One family of soluble factors that is becoming increasingly associated with pro-tumoral phenotypes within tumor microenvironments is that of the migration inhibitory factor family which includes its namesake, MIF, and its only known family member, D-dopachrome tautomerase (D-DT). This review seeks to highlight our current understanding of the relative contributions of a variety of immune and non-immune tumor stromal cell populations and, within those contexts, will summarize the literature associated with MIF and/or D-DT.
• Yaddanapudi, K., Mitchell, R. A., & Eaton, J. W. (2013). Cancer vaccines: Looking to the future. Oncoimmunology, 2(3), e23403.
  More info

  These are exciting times for the field of cancer immunotherapy. Although the clinical efficacy of monoclonal antibodies has been demonstrated since the early 1990s, the therapeutic profile of other immunotherapeutic approaches-especially vaccines-has not yet been formally clarified. However, the recent success of several immunotherapeutic regimens in cancer patients has boosted the development of this treatment modality. These achievements stemmed from recent scientific advances demonstrating the tolerogenic nature of cancer and the fundamental role of the tumor immune microenvironment in the suppression of antitumor immunity. New immunotherapeutic strategies against cancer attempt to promote protective antitumor immunity while disrupting the immunoregulatory circuits that contribute to tumor tolerance. Cancer vaccines differ from other anticancer immunotherapeutics in that they initiate the dynamic process of activating the immune system so as to successfully re-establish a state of equilibrium between tumor cells and the host. This article reviews recent clinical trials involving several different cancer vaccines and describes some of the most promising immunotherapeutic approaches that harness antitumor T-cell responses. In addition, we describe strategies whereby cancer vaccines can be exploited in combination with other therapeutic approach to overcome-in a synergistic fashion-tumor immunoevasion. Finally, we discuss prospects for the future development of broad spectrum prophylactic anticancer vaccines.
• Yaddanapudi, K., Putty, K., Rendon, B. E., Lamont, G. J., Faughn, J. D., Satoskar, A., Lasnik, A., Eaton, J. W., & Mitchell, R. A. (2013). Control of tumor-associated macrophage alternative activation by macrophage migration inhibitory factor. Journal of immunology (Baltimore, Md. : 1950), 190(6), 2984-93.
  More info

  Tumor stromal alternatively activated macrophages are important determinants of antitumor T lymphocyte responses, intratumoral neovascularization, and metastatic dissemination. Our recent efforts to investigate the mechanism of macrophage migration inhibitory factor (MIF) in antagonizing antimelanoma immune responses reveal that macrophage-derived MIF participates in macrophage alternative activation in melanoma-bearing mice. Both peripheral and tumor-associated macrophages (TAMs) isolated from melanoma bearing MIF-deficient mice display elevated proinflammatory cytokine expression and reduced anti-inflammatory, immunosuppressive, and proangiogenic gene products compared with macrophages from tumor-bearing MIF wild-type mice. Moreover, TAMs and myeloid-derived suppressor cells from MIF-deficient mice exhibit reduced T lymphocyte immunosuppressive activities compared with those from their wild-type littermates. Corresponding with reduced tumor immunosuppression and neo-angiogenic potential by TAMs, MIF deficiency confers protection against transplantable s.c. melanoma outgrowth and melanoma lung metastatic colonization. Finally, we report for the first time, to our knowledge, that our previously discovered MIF small molecule antagonist, 4-iodo-6-phenylpyrimidine, recapitulates MIF deficiency in vitro and in vivo, and attenuates tumor-polarized macrophage alternative activation, immunosuppression, neoangiogenesis, and melanoma tumor outgrowth. These studies describe an important functional contribution by MIF to TAM alternative activation and provide justification for immunotherapeutic targeting of MIF in melanoma patients.
• Yaddanapudi, K., & Eaton, J. W. (2012). Multi-peptide immunotherapeutic vaccine for renal cell carcinoma: getting the troops all worked up. Translational andrology and urology, 1(4), 229-233.

Presentations

• Seckeler, M., Chatterjee, A., Meziab, O., Camarena, M., Chandra, S., Yaddanapudi, K., Hoyer, A., Caryl, N., Seckeler, M., Chatterjee, A., Meziab, O., Camarena, M., Chandra, S., Yaddanapudi, K., Hoyer, A., & Caryl, N. (2023, May). Not every TIA is a PFO – the importance of other shunts. The Society for Cardiovascular Angiography and Interventions 2023 Scientific Sessions. Phoenix, Arizona.
• Yaddanapudi, K. (2019, Sept). Cardiac PET MRI Clinical applications. NASCI.
• Yaddanapudi, K. (2021, March 2021). Imaging of left atrium. Society Thoracic Radiology. Online.
• Yaddanapudi, K. (2021, September). Imaging Left Atrial Occlusion Devices. North American Society Cardiovascular Imaging Annual Meeting. online.
• Yaddanapudi, K. (2019, March). Cardiac PET MRI Protocols and how we do it. STR.