Dr. Juliano D Paccez

CTO, Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil

Scientific Researcher

Dr. Juliano D Paccez

CTO, Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil

Scientific Researcher

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Academic Career Length

21Years (2006-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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3 May 2013 in International Journal of Cancer

Journal Article

The receptor tyrosine kinase Axl in cancer: Biological functions and therapeutic implications

Juliano D Paccez

Matjaz Vogelsang

M. Iqbal Parker

Luiz Zerbini

The receptor tyrosine kinase Axl has been implicated in the malignancy of different types of cancer. Emerging evidence of Axl upregulation in numerous cancers, as well as reports demonstrating that its inhibition blocks tumor formation in animal models, highlight the importance of Axl as a new potential therapeutic target. Furthermore, recent data demonstrate that Axl plays a pivotal role in resistance to chemotherapeutic regimens. In this review we discuss the functions of Axl and its regulation and role in cancer development, resistance to therapy, and its importance as a potential drug target, focusing on acute myeloid leukemia, breast, prostate and non‐small cell lung cancers.

12 March 2012 in Oncogene

Journal Article

The receptor tyrosine kinase Axl is an essential regulator of prostate cancer proliferation and tumor growth and represents a new therapeutic target

Juliano D Paccez

G J Vasques

R G Correa

J F Vasconcellos

K Duncan

Luiz Zerbini

Deregulation of the receptor tyrosine kinase Axl has been implicated in the progression of several human cancers. However, the role of Axl in prostate cancer remains poorly understood, and the therapeutic efficacy of Axl targeting remains untested. In this report we identified Axl as a new therapeutic target for prostate cancer. Axl is consistently overexpressed in prostate cancer cell lines and human prostate tumors. Interestingly, the blockage of Axl gene expression strongly inhibits proliferation, migration, invasion and tumor growth. Furthermore, inhibition of Axl expression by small interfering RNA regulates a transcriptional program of genes involved in cell survival, strikingly all connected to the nuclear factor-κB pathway. Additionally, blockage of Axl expression leads to inhibition of Akt, IKKα and IκBα phosphorylation, increasing IκBα expression and stability. Furthermore, induction of Akt phosphorylation by insulin-like growth factor 1 in Axl knockdown cells restores Akt activity and proliferation. Taken together, our results establish an unambiguous role for Axl in prostate cancer tumorigenesis with implications for prostate cancer treatment.

25 March 2021 in Cancers

Journal Article

The Role of the Receptor Tyrosine Kinase Axl in Carcinogenesis and Development of Therapeutic Resistance: An Overview of Molecular Mechanisms and Future Applications

Martha Wium

Aderonke F. Ajayi-Smith

Juliano D Paccez

Luiz Zerbini

Resistance to chemotherapeutic agents by cancer cells has remained a major obstacle in the successful treatment of various cancers. Numerous factors such as DNA damage repair, cell death inhibition, epithelial–mesenchymal transition, and evasion of apoptosis have all been implicated in the promotion of chemoresistance. The receptor tyrosine kinase Axl, a member of the TAM family (which includes TYRO3 and MER), plays an important role in the regulation of cellular processes such as proliferation, motility, survival, and immunologic response. The overexpression of Axl is reported in several solid and hematological malignancies, including non-small cell lung, prostate, breast, liver and gastric cancers, and acute myeloid leukaemia. The overexpression of Axl is associated with poor prognosis and the development of resistance to therapy. Reports show that Axl overexpression confers drug resistance in lung cancer and advances the emergence of tolerant cells. Axl is, therefore, an important candidate as a prognostic biomarker and target for anticancer therapies. In this review, we discuss the consequence of Axl upregulation in cancers, provide evidence for its role in cancer progression and the development of drug resistance. We will also discuss the therapeutic potential of Axl in the treatment of cancer.

13 June 2017 in Mediators of Inflammation

Journal Article

Antifungal Resistance, Metabolic Routes as Drug Targets, and New Antifungal Agents: An Overview about Endemic Dimorphic Fungi

Juliana Alves Parente-Rocha

Alexandre Melo Bailão

Diseases caused by fungi can occur in healthy people, but immunocompromised patients are the major risk group for invasive fungal infections. Cases of fungal resistance and the difficulty of treatment make fungal infections a public health problem. This review explores mechanisms used by fungi to promote fungal resistance, such as the mutation or overexpression of drug targets, efflux and degradation systems, and pleiotropic drug responses. Alternative novel drug targets have been investigated; these include metabolic routes used by fungi during infection, such as trehalose and amino acid metabolism and mitochondrial proteins. An overview of new antifungal agents, including nanostructured antifungals, as well as of repositioning approaches is discussed. Studies focusing on the development of vaccines against antifungal diseases have increased in recent years, as these strategies can be applied in combination with antifungal therapy to prevent posttreatment sequelae. Studies focused on the development of a pan-fungal vaccine and antifungal drugs can improve the treatment of immunocompromised patients and reduce treatment costs.

19 February 2019 in Oncogenesis

Journal Article

Dihydroartemisinin inhibits prostate cancer via JARID2/miR-7/miR-34a-dependent downregulation of Axl

Juliano D Paccez

Kristal Duncan

Durairaj Sekar

Ricardo G. Correa

Yihong Wang

Luiz Zerbini

Axl expression is deregulated in several cancer types, predicts poor overall patient survival and is linked to resistance to drug therapy. Here, we evaluated a library of natural compounds for inhibitors of Axl and identified dihydroartemisinin, the active principle of the anti-malarial drug artemisinin, as an Axl-inhibitor in prostate cancer. Dihydroartemisinin blocks Axl expression leading to apoptosis, decrease in cell proliferation, migration, and tumor development of prostate cancer cells. Dihydroartemisinin treatment synergizes with docetaxel, a standard of care in metastatic prostate cancer increasing overall survival of mice with human xenografts. Dihydroartemisinin control of miR-34a and miR-7 expression leads to inhibition of Axl expression in a process at least partially dependent on regulation of chromatin via methylation of histone H3 lysine 27 residues by Jumonji, AT-rich interaction domain containing 2 (JARID2), and the enhancer of zeste homolog 2. Our discovery of a previously unidentified miR-34a/miR-7/JARID2 pathway controlling dihydroartemisinin effects on Axl expression and inhibition of cancer cell proliferation, migration, invasion, and tumor formation provides new molecular mechanistic insights into dihydroartemisinin anticancer effect on prostate cancer with potential therapeutic implications.

12 October 2018 in Cells

Journal Article

The Dual Role of TAM Receptors in Autoimmune Diseases and Cancer: An Overview

Martha Wium

Juliano D Paccez

Luiz Zerbini

Receptor tyrosine kinases (RTKs) regulate cellular processes by converting signals from the extracellular environment to the cytoplasm and nucleus. Tyro3, Axl, and Mer (TAM) receptors form an RTK family that plays an intricate role in tissue maintenance, phagocytosis, and inflammation as well as cell proliferation, survival, migration, and development. Defects in TAM signaling are associated with numerous autoimmune diseases and different types of cancers. Here, we review the structure of TAM receptors, their ligands, and their biological functions. We discuss the role of TAM receptors and soluble circulating TAM receptors in the autoimmune diseases systemic lupus erythematosus (SLE) and multiple sclerosis (MS). Lastly, we discuss the effect of TAM receptor deregulation in cancer and explore the therapeutic potential of TAM receptors in the treatment of diseases.

About Me

Translational Oncology researcher with over 15 years of experience in cancer molecular biology, genomics, and proteomics. Holds a B.Sc. in Biological Sciences from the University of São Paulo (IB–USP, 2002) and a Ph.D. in Microbiology from the Institute of Biomedical Sciences, USP (ICB–USP, 2007). Completed postdoctoral training at ICB–USP (2008–2009) and at the International Centre for Genetic Engineering and Biotechnology (ICGEB, South Africa, 2011–2014), focusing on tumor molecular biology, oncogene-driven signaling—particularly tyrosine kinase receptors—drug resistance, and cancer-related pathways. Served as Visiting Professor at the Federal University of Goiás (2016–2020), teaching postgraduate courses and supervising students in the Genetics and Molecular Biology Program (PGBM–ICB–UFG). Worked as a Clinical Research Associate at InTrials (2020–2021). Previously Senior Scientist at ICGEB (South Africa), leading multi-omics research in prostate cancer and hepatocellular carcinoma, with emphasis on mechanisms of therapeutic resistance. Author of peer-reviewed publications, active reviewer for international journals, and recipient of competitive funding (NRF–SA, FAPEG/CNPq, FAPESP, Yamagiwa–Yoshida). Currently Staff Scientist at the Experimental Oncology Laboratory, Translational Oncology Research Center (CTO), ICESP, developing integrative omics approaches to investigate therapeutic resistance, tumor metabolism, and microRNA regulation.

Dr. Juliano D Paccez

Dr. Juliano D Paccez

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