Mary J C Hendrix

Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, United States

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Publications (291)1542.43 Total impact

  • No preview · Article · May 2016 · Stem Cells and Development
  • [Show abstract] [Hide abstract] ABSTRACT: Triple-negative breast cancer (TNBC) represents an aggressive cancer subtype characterized by the lack of expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The independence of TNBC from these growth promoting factors eliminates the efficacy of therapies which specifically target them, and limits TNBC patients to traditional systemic neo/adjuvant chemotherapy. To better understand the growth advantage of TNBC - in the absence of ER, PR and HER2, we focused on the embryonic morphogen Nodal (associated with the cancer stem cell phenotype), which is re-expressed in aggressive breast cancers. Most notably, our previous data demonstrated that inhibition of Nodal signaling in breast cancer cells reduces their tumorigenic capacity. Furthermore, inhibiting Nodal in other cancers has resulted in improved effects of chemotherapy, although the mechanisms for this remain unknown. Thus, we hypothesized that targeting Nodal in TNBC cells in combination with conventional chemotherapy may improve efficacy and represent a potential new strategy. Our preliminary data demonstrate that Nodal is highly expressed in TNBC when compared to invasive hormone receptor positive samples. Treatment of Nodal expressing TNBC cell lines with a neutralizing anti-Nodal antibody reduces the viability of cells that had previously survived treatment with the anthracycline doxorubicin. We show that inhibiting Nodal may alter response mechanisms employed by cancer cells undergoing DNA damage. These data suggest that development of therapies which target Nodal in TNBC may lead to additional treatment options in conjunction with chemotherapy regimens - by altering signaling pathways critical to cellular survival.
    No preview · Article · Mar 2016 · Cell cycle (Georgetown, Tex.)
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    [Show abstract] [Hide abstract] ABSTRACT: Expression of Nodal, a Transforming Growth Factor-beta (TGF-β) related growth factor, is associated with aggressive melanoma. Nodal expression in adult dysplastic nevi may predict the development of aggressive melanoma in some patients. A subset of pediatric patients diagnosed with giant or large congenital melanocytic nevi (LCMN) has shown increased risk for development of melanoma. Here, we investigate whether Nodal expression can help identify the rare cases of LCMN that develop melanoma and shed light on why the majority of these patients do not. Immunohistochemistry (IHC) staining results show varying degree of Nodal expression in pediatric dysplastic nevi and LCMN. Moreover, median scores from Nodal IHC expression analysis were not significantly different between these two groups. Additionally, none of the LCMN patients in this study developed melanoma, regardless of Nodal IHC levels. Co-culture experiments revealed reduced tumor growth and lower levels of Nodal and its signaling molecules P-SMAD2 and P-ERK1/2 when melanoma cells were grown in vivo or in vitro with normal melanocytes. The same was observed in melanoma cells cultured with melanocyte conditioned media containing pigmented melanocyte derived melanosomes (MDM). Since MDM contain molecules capable of inactivating radical oxygen species, to investigate potential anti-oxidant effect of MDM on Nodal expression and signaling in melanoma, melanoma cells were treated with either N-acetyl-l-cysteine (NAC), a component of the anti-oxidant glutathione or synthetic melanin, which in addition to providing pigmentation can also exert free radical scavenging activity. Melanoma cells treated with NAC or synthetic melanin showed reduced levels of Nodal, P-SMAD2 and P-ERK1/2 compared to untreated melanoma cells. Thus, the potential role for Nodal in melanoma development in LCMN is less evident than in adult dysplastic nevi possibly due to melanocyte cross-talk in LCMN capable of offsetting or delaying the pro-melanoma effects of Nodal via anti-oxidant effects of MDM.
    Full-text · Article · Mar 2016 · International Journal of Molecular Sciences
  • [Show abstract] [Hide abstract] ABSTRACT: The transforming growth factor beta (TGFβ) superfamily member Nodal is an established regulator of early embryonic development, with primary roles in endoderm induction, left-right asymmetry, and primitive streak formation. Nodal signals through TGFβ family receptors at the plasma membrane and induces signaling cascades leading to diverse transcriptional regulation. While conceptually simple, the regulation of Nodal and its molecular effects are profoundly complex and context dependent. Pioneering work by developmental biologists has characterized the signaling pathways, regulatory components, and provided detailed insight into the mechanisms by which Nodal mediates changes at the cellular and organismal levels. Nodal is also an important factor in maintaining pluripotency of embryonic stem cells through regulation of core transcriptional programs. Collectively, this work has led to an appreciation for Nodal as a powerful morphogen capable of orchestrating multiple cellular phenotypes. Although Nodal is not active in most adult tissues, its reexpression and signaling have been linked to multiple types of human cancer, and Nodal has emerged as a driver of tumor growth and cellular plasticity. In vitro and in vivo experimental evidence has demonstrated that inhibition of Nodal signaling reduces cancer cell aggressive characteristics, while clinical data have established associations with Nodal expression and patient outcomes. As a result, there is great interest in the potential targeting of Nodal activity in a therapeutic setting for cancer patients that may provide new avenues for suppressing tumor growth and metastasis. In this review, we evaluate our current understanding of the complexities of Nodal function in cancer and highlight recent experimental evidence that sheds light on the therapeutic potential of its inhibition.
    No preview · Article · Mar 2016 · Cancer and metastasis reviews
  • [Show abstract] [Hide abstract] ABSTRACT: In 1999, the American Journal of Pathology published an article, entitled “Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry” by Maniotis and colleagues, which ignited a spirited debate for several years and earned the journal’s distinction of a “citation classic” (Maniotis et al., 1999). Tumor cell vasculogenic mimicry (VM), also known as vascular mimicry, describes the plasticity of aggressive cancer cells forming de novo vascular networks and is associated with the malignant phenotype and poor clinical outcome. The tumor cells capable of VM share the commonality of a stem cell-like, transendothelial phenotype, which may be induced by hypoxia. Since its introduction as a novel paradigm for melanoma tumor perfusion, many studies have contributed new findings illuminating the underlying molecular pathways supporting VM in a variety of tumors, including carcinomas, sarcomas, glioblastomas, astrocytomas, and melanomas. Of special significance is the lack of effectiveness of angiogenesis inhibitors on tumor cell VM, suggesting a selective resistance by this phenotype to conventional therapy. Facilitating the functional plasticity of tumor cell VM are key proteins associated with vascular, stem cell, extracellular matrix, and hypoxia-related signaling pathways -- each deserving serious consideration as potential therapeutic targets and diagnostic indicators of the aggressive, metastatic phenotype. This review highlights seminal findings pertinent to VM, including the effects of a novel, small molecular compound, CVM-1118, currently under clinical development to target VM, and illuminates important molecular pathways involved in the suppression of this plastic, aggressive phenotype, using melanoma as a model.
    No preview · Article · Jan 2016 · Pharmacology [?] Therapeutics
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    [Show abstract] [Hide abstract] ABSTRACT: Nodal is highly expressed in various human malignancies, thus supporting the rationale for exploring Nodal as a therapeutic target. Here, we describe the effects of a novel monoclonal antibody (mAb), 3D1, raised against human Nodal. In vitro treatment of C8161 human melanoma cells with 3D1 mAb shows reductions in anchorage-independent growth and vasculogenic network formation. 3D1 treated cells also show decreases of Nodal and downstream signaling molecules, P-Smad2 and PERK and of P-H3 and CyclinB1, with an increase in p27. Similar effects were previously reported in human breast cancer cells where Nodal expression was generally down-regulated; following 3D1 mAb treatment, both Nodal and P-H3 levels are reduced. Noteworthy is the reduced growth of human melanoma xenografts in Nude mice treated with 3D1 mAb, where immunostaining of representative tumor sections show diminished P-Smad2 expression. Similar effects both in vitro and in vivo were observed in 3D1 treated A375SM melanoma cells harboring the active BRAF(V600E) mutation compared to treatments with IgG control or a BRAF inhibitor, dabrafenib. Finally, we describe a 3D1-based ELISA for the detection of Nodal in serum samples from cancer patients. These data suggest the potential of 3D1 mAb for selecting and targeting Nodal expressing cancers.
    Full-text · Article · Oct 2015 · Oncotarget
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    [Show abstract] [Hide abstract] ABSTRACT: Nodal is a potent embryonic morphogen belonging to the TGF-β superfamily. Typically, it also binds to the ALK4/ActRIIB receptor complex in the presence of the co-receptor Cripto-1. Nodal expression is physiologically restricted to embryonic tissues and human embryonic stem cells, is absent in normal cells but re-emerges in several human cancers, including melanoma, breast, and colon cancer. Our aim was to obtain mAbs able to recognize Nodal on a major CBR (Cripto-Binding-Region) site and to block the OPEN ACCESS Int. J. Mol. Sci. 2015, 16 21343 Cripto-1-mediated signalling. To achieve this, antibodies were raised against hNodal(44–67) and mAbs generated by the hybridoma technology. We have selected one mAb, named 3D1, which strongly associates with full-length rhNodal (KD 1.4 nM) and recognizes the endogenous protein in a panel of human melanoma cell lines by western blot and FACS analyses. 3D1 inhibits the Nodal-Cripto-1 binding and blocks Smad2/3 phosphorylation. Data suggest that inhibition of the Nodal-Cripto-1 axis is a valid therapeutic approach against melanoma and 3D1 is a promising and interesting agent for blocking Nodal-Cripto mediated tumor development. These findings increase the interest for Nodal as both a diagnostic and prognostic marker and as a potential new target for therapeutic intervention.
    Full-text · Article · Sep 2015 · International Journal of Molecular Sciences
  • [Show abstract] [Hide abstract] ABSTRACT: Cripto-1 (CR-1) is a multifunctional embryonic protein that is re-expressed during inflammation, wound repair, and malignant transformation. CR-1 can function either as a tethered co-receptor or shed as a free ligand underpinning its flexible role in cell physiology. CR-1 has been shown to mediate cell growth, migration, invasion, and induce epithelial to mesenchymal transition (EMT). The main signaling pathways mediating CR-1 effects include Nodal-dependent (Smad2/3) and Nodal-independent (Src/p44/42/Akt) signaling transduction pathways. In addition, there are several naturally occurring binding partner proteins (BPPs) for CR-1 that can either agonize or antagonize its bioactivity. We will review the collective role of CR-1 as an extracellular protein, discuss caveats to consider in developing a quantitation assay, define possible mechanistic avenues applicable for drug discovery, and report on our experimental approaches to overcome these problematic issues.
    No preview · Article · Sep 2015 · Connective tissue research
  • No preview · Article · Aug 2015 · Cancer Research
  • Mary J C Hendrix
    No preview · Article · Apr 2015 · Nature
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    [Show abstract] [Hide abstract] ABSTRACT: There is growing evidence and a consensus in the field that most pediatric brain tumors originate from stem cells, of which radial glial cells constitute a subtype. Here we show that orthotopic transplantation of human radial glial (RG) cells to the subventricular zone of the 3rd ventricle--but not to other transplantation sites--of the brain in immunocompromised NOD-SCID mice, gives rise to tumors that have the hallmarks of CNS primitive neuroectodermal tumors (PNETs). The resulting mouse model strikingly recapitulates the phenotype of PNETs. Importantly, the observed tumorigenic transformation was accompanied by aspects of an epithelial to mesenchymal transition (EMT)-like process. It is also noteworthy that the tumors are highly invasive, and that they effectively recruit mouse endothelial cells for angiogenesis. These results are significant for several reasons. First, they show that malignant transformation of radial glial cells can occur in the absence of specific mutations or inherited genomic alterations. Second, they demonstrate that the same radial glial cells may either give rise to brain tumors or differentiate normally depending upon the microenvironment of the specific region of the brain to which the cells are transplanted. In addition to providing a prospect for drug screening and development of new therapeutic strategies, the resulting mouse model of PNETs offers an unprecedented opportunity to identify the cancer driving molecular alterations and the microenvironmental factors that are responsible for committing otherwise normal radial glial cells to a malignant phenotype.
    Full-text · Article · Mar 2015 · PLoS ONE
  • [Show abstract] [Hide abstract] ABSTRACT: Metastatic melanoma is a highly aggressive skin cancer with a poor prognosis. Despite a complete response in fewer than 5% of patients, the chemotherapeutic agent dacarbazine (DTIC) remains the reference drug after almost 40 years. More recently, FDA-approved drugs have shown promise but patient outcome remains modest, predominantly due to drug resistance. As such, combinatorial targeting has received increased attention, and will advance with the identification of new molecular targets. One attractive target for improving melanoma therapy is the growth factor Nodal, whose normal expression is largely restricted to embryonic development, but is reactivated in metastatic melanoma. In this study, we sought to determine how Nodal-positive human melanoma cells respond to DTIC treatment and to ascertain whether targeting Nodal in combination with DTIC would be more effective than monotherapy. A single treatment with DTIC inhibited cell growth but did not induce apoptosis. Rather than reducing Nodal expression, DTIC increased the size of the Nodal-positive subpopulation, an observation coincident with increased cellular invasion. Importantly, clinical tissue specimens from patients with melanomas refractory to DTIC therapy stained positive for Nodal expression, both in pre- and post-DTIC tumors, underscoring the value of targeting Nodal. In vitro, anti-Nodal antibodies alone had some adverse effects on proliferation and apoptosis, but combining DTIC treatment with anti-Nodal antibodies decreased cell growth and increased apoptosis synergistically, at concentrations incapable of producing meaningful effects as monotherapy. Targeting Nodal in combination with DTIC therapy holds promise for the treatment of metastatic melanoma. Mol Cancer Res; 1-11. ©2015 AACR. ©2015 American Association for Cancer Research.
    No preview · Article · Mar 2015 · Molecular Cancer Research
  • [Show abstract] [Hide abstract] ABSTRACT: Primary uveal melanoma tumors have been shown to harbor activating mutations in the heterotrimeric G-alpha protein subunits GNAQ or GNA11 genes in approximately 85% of samples.(Van Raamsdonk et al., 2009, Van Raamsdonk et al., 2010) Mutations in GNAQ or GNA11 are mutually exclusive, and result in amino acid changes at either the R183 or Q209 sites. GNAQ or GNA11 mutations have also been identified in uveal melanoma liver metastases suggesting that the metastatic cells in the liver are derived from primary tumor cell clones with these mutations.(Carvajal et al. 2014) In addition, the many uveal melanoma cell lines derived from metastatic sites also harbor GNAQ or GNA11 mutations.(Griewank et al., 2012)This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2014 · Pigment Cell & Melanoma Research
  • [Show abstract] [Hide abstract] ABSTRACT: The Ras-ERK pathway is deregulated in approximately a third of human cancers, particularly those of epithelial origin. In aggressive, triple-negative, basal-like breast cancers, most tumors display increased MEK and ERK phosphorylation and exhibit a gene expression profile characteristic of Kras or EGFR mutant tumors; however, Ras family genetic mutations are uncommon in triple-negative breast cancer and EGFR mutations account for only a subset of these tumors. Therefore, the upstream events that activate MAPK signaling and promote tumor aggression in triple-negative breast cancers remain poorly defined. We have previously shown that a secreted TGF-β family signaling ligand, Nodal, is expressed in breast cancer in correlation with disease progression. Here we highlight key findings demonstrating that Nodal is required in aggressive human breast cancer cells to activate ERK signaling and downstream tumorigenic phenotypes both in vitro and in vivo. Experimental knockdown of Nodal signaling downregulates ERK activity, resulting in loss of c-myc, upregulation of p27, G1 cell cycle arrest, increased apoptosis and decreased tumorigenicity. The data suggest that ERK activation by Nodal signaling regulates c-myc and p27 proteins post-translationally and that this cascade is essential for aggressive breast tumor behavior in vivo. As the MAPK pathway is an important target for treating triple-negative breast cancers, upstream Nodal signaling may represent a promising target for breast cancer diagnosis and combined therapies aimed at blocking ERK pathway activation.
    No preview · Article · Dec 2014 · Seminars in Cancer Biology
  • [Show abstract] [Hide abstract] ABSTRACT: The significant role of the embryonic morphogen Nodal in maintaining the pluripotency of embryonic stem cells is well documented. Interestingly, the recent discovery of Nodal's re-expression in several aggressive and metastatic cancers has highlighted its critical role in self renewal and maintenance of the stem cell-like characteristics of tumor cells, such as melanoma. However, the key TGFβ/Nodal signaling component(s) governing Nodal's effects in metastatic melanoma remain mostly unknown. By employing receptor profiling at the mRNA and protein level(s), we made the novel discovery that embryonic stem cells and metastatic melanoma cells share a similar repertoire of Type I serine/threonine kinase receptors, but diverge in their Type II receptor expression. Ligand:receptor crosslinking and native gel binding assays indicate that metastatic melanoma cells employ the heterodimeric TGFβ receptor I/TGFβ receptor II (TGFβRI/TGFβRII) for signal transduction, whereas embryonic stem cells use the Activin receptors I and II (ACTRI/ACTRII). This unexpected receptor usage by tumor cells was tested by: neutralizing antibody to block its function; and transfecting the dominant negative receptor to compete with the endogenous receptor for ligand binding. Furthermore, a direct biological role for TGFβRII was found to underlie vasculogenic mimicry (VM), an endothelial phenotype contributing to vascular perfusion and associated with the functional plasticity of aggressive melanoma. Collectively, these findings reveal the divergence in Nodal signaling between embryonic stem cells and metastatic melanoma that can impact new therapeutic strategies targeting the re-emergence of embryonic pathways. © 2014 Wiley Periodicals, Inc.
    No preview · Article · Oct 2014 · International Journal of Cancer
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    [Show abstract] [Hide abstract] ABSTRACT: Unlabelled: Patients with metastatic disease face high rates of mortality with a paucity of therapeutic options. Protein-based therapeutics provide advantages over traditional chemotherapy through increased specificity, decreased immune impairment, and more direct means of delivery. However, development is often hindered because of insufficient knowledge about protein processing by cells when exogenously applied. This study focuses on recombinant Maspin (rMaspin), a serine protease inhibitor (SERPINB5), which alters invasive properties when directly applied to cancer cells. Previous evidence suggests differences in the effects of rMaspin treatment when compared with endogenous reexpression, with little explanation for these discrepancies. A leading hypothesis is that exogenously applied rMaspin is subject to different regulatory and/or processing mechanisms in cancer cells when compared with endogenous expression. Therefore, a more detailed understanding of the mechanisms of internalization and subcellular trafficking of rMaspin is needed to guide future translational development. We describe the molecular trafficking of rMaspin in cytoplasmic vesicles of the endosomal/lysosomal pathway and characterize its uptake by multiple endocytic mechanisms. Time-lapse laser scanning confocal microscopy shows the uptake, in real time, of dye-labeled rMaspin in cancer cells. This study indicates that cellular processing of rMaspin plays a key role by affecting its biologic activity and highlights the need for new approaches aimed at increasing the availability of rMaspin when used to treat cancer. Implications: Novel characterization of internalization and subcellular trafficking of rMaspin provides new insights for future therapeutic development.
    Full-text · Article · Sep 2014 · Molecular Cancer Research
  • Lars Ahrlund-Richter · Mary J C Hendrix
    No preview · Article · Aug 2014 · Seminars in Cancer Biology
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    [Show abstract] [Hide abstract] ABSTRACT: The post-lactational regression of mammary gland is a complex multi-step process designed to conserve the biological function of the gland for next pregnancy. This developmental stage is a biological intrigue with great relevance to breast cancer research, and thus has been the subject of intensive scrutiny. Multipronged studies (microarray, proteomics profiling, animal knock-out models) have provided a repertoire of genes critical to involution. However, the caveat of these approaches remains in their failure to reveal post-translational modification(s), an emerging and critical aspect of gene regulation in developmental processes and mammary gland remodeling. The massive surge in the lysosomal enzymes concurrent with the onset of involution has been known for decades, and considered essential for "clearance" purposes. However, functional significance of these enzymes in diverse biological processes distinct from their proteolytic activity is just emerging. Studies from our laboratory had indicated specific post-translational modifications of the aspartyl endopeptidase Cathepsin D (CatD) at distinct stages mammary gland development. This study addresses the biological significance of these modifications in the involution process, and reveals that post-translational modifications drive CatD into the nucleus to cleave Histone 3. The cleavage of Histone 3 has been associated with cellular differentiation and could be critical instigator of involution process. From functional perspective, deregulated expression and increased secretion of CatD are associated with aggressive and metastatic phenotype of breast cancer. Thus unraveling CatD's physiological functions in mammary gland development will bridge the present gap in understanding its pro-tumorigenic/metastatic functions, and assist in the generation of tailored therapeutic approaches.
    Full-text · Article · Jul 2014 · PLoS ONE
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    [Show abstract] [Hide abstract] ABSTRACT: Several studies have shown that cancer niche can perform an active role in the regulation of tumor cell maintenance and progression through extracellular vesicles-based intercellular communication. However, it has not been reported whether this vesicle-mediated communication affects the malignant transformation of normal stem cells/progenitors. We have previously reported that the conditioned medium derived from the mouse Lewis Lung Carcinoma (LLC) cell line can convert mouse induced pluripotent stem cells (miPSCs) into cancer stem cells (CSCs), indicating that normal stem cells when placed in an aberrant microenvironment can give rise to functionally active CSCs. Here, we focused on the contribution of tumor-derived extracellular vesicles (tEVs) that are secreted from LLC cells to induce the transformation of miPSCs into CSCs. We isolated tEVs from the conditioned medium of LLC cells, and then the differentiating miPSCs were exposed to tEVs for 4 weeks. The resultant tEV treated cells (miPS-LLCev) expressed Nanog and Oct3/4 proteins comparable to miPSCs. The frequency of sphere formation of the miPS-LLCev cells in suspension culture indicated that the self-renewal capacity of the miPS-LLCev cells was significant. When the miPS-LLCev cells were subcutaneously transplanted into Balb/c nude mice, malignant liposarcomas with extensive angiogenesis developed. miPS-LLCevPT and miPS-LLCevDT, the cells established from primary site and disseminated liposarcomas, respectively, showed their capacities to self-renew and differentiate into adipocytes and endothelial cells. Moreover, we confirmed the secondary liposarcoma development when these cells were transplanted. Taken together, these results indicate that miPS-LLCev cells possess CSC properties. Thus, our current study provides the first evidence that tEVs have the potential to induce CSC properties in normal tissue stem cells/progenitors.
    Full-text · Article · Jul 2014 · Journal of Cancer
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    Zhila Khalkhali-Ellis · Mary J.C. Hendrix
    [Show abstract] [Hide abstract] ABSTRACT: Since its discovery as a lysosomal hydrolase, Cathepsin D (CatD) has been the subject of intensive scrutiny by numerous scientists. Those accumulated efforts have defined its biosynthetic pathway, structure, and companion proteins in the context of its perceived “house keeping” function. However, in the past two decades CatD has emerged as a multifunctional enzyme, involved in myriad biological processes beyond its original “housekeeping” role. CatD is responsible for selective and limited cleavage (quite distinct from non-specific protein degradation) of particular substrates vital to proper cellular function. These proteolytic events are critical in the control of biological processes, including cell cycle progression, differentiation and migration, morphogenesis and tissue remodeling, immunological processes, ovulation, fertilization, neuronal outgrowth, angiogenesis, and apoptosis. Consistent with the biological relevance of CatD, its deficiency, altered regulation or post-translational modification underlie important pathological conditions such as cancer, atherosclerosis, neurological and skin disorders. Specifically, deregulated synthesis, post-translational modifications and hyper-secretion of CatD, along with its mitogenic effects, are established hallmarks of cancer. More importantly, but less studied, is its significance in regulating the sensitivity to anticancer drugs. This review outlines CatD’s post-translational modifications, cellular trafficking, secretion and protein binding partners in normal mammary gland, and restates the “site-specific” function of CatD which is most probably dictated by its post-translational modifications and binding partners. Noteworthy, CatD’s association with one of its binding partners in the context of drug sensitivity is highlighted, with the optimism that it could contribute to the development of more effective chemotherapeutic agent(s) tailored for individual patients.
    Preview · Article · Jul 2014 · Biology and Medicine

Publication Stats

19k Citations
1,542.43 Total Impact Points

Institutions

  • 2006-2015
    • Ann & Robert H. Lurie Children's Hospital of Chicago
      Chicago, Illinois, United States
    • Children's Memorial Hospital
      Chicago, Illinois, United States
  • 2005-2014
    • Northwestern University
      • Feinberg School of Medicine
      Evanston, Illinois, United States
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2008
    • The University of Western Ontario
      • Department of Anatomy and Cell Biology
      London, Ontario, Canada
  • 2002-2006
    • University of Iowa
      • • Department of Biochemistry
      • • Department of Anatomy and Cell Biology
      Iowa City, IA, United States
  • 2003
    • The Scripps Research Institute
      La Jolla, California, United States
  • 2001
    • Federation of American Societies for Experimental Biology
      Maryland, United States
  • 1991-1992
    • The University of Arizona
      • College of Medicine
      Tucson, Arizona, United States
    • Vanderbilt University
      • Vanderbilt Center for Stem Cell Biology
      Nashville, MI, United States
  • 1990
    • Arizona Research Center
      Phoenix, Arizona, United States