Julio A. Camarero Palao, PhD

Professor

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Overview

Julio A. Camarero started his studies in chemistry at the University of Barcelona (Spain), received his Master of Science degree in 1992, and finished his PhD thesis there in 1996. Afterward, he joined the group of Prof. Tom W. Muir at Rockefeller University as a Burroughs Wellcome Fellow, where he contributed to the development of new chemoselective ligation techniques for the chemical engineering of proteins. In 2000, he moved to the Lawrence Livermore National Laboratory as a Distinguished Lawrence Fellow, becoming a senior scientist and head of the Protein Chemistry and Engineering Laboratory in 2003. He joined the University of Southern California in 2008 as an Associate Professor.

His current research interests are focused on the development of new chemical biology approaches using protein splicing and synthetic protein chemistry to study biological processes involved in cancer and bacterial pathogenicity and how they can be modulated or inhibited by small Cys-knotted microproteins called cyclotides. Camarero has authored over 120 peer-reviewed publications and four invited book chapters. His lab is strongly funded by federal (NIH, DoD-CMDRP) and private foundation (American Cancer Society, Melanoma Research Alliance, American Lung Association) sponsors, among others.

Dr. Camarero is a prominent researcher known for his work in protein engineering, chemical biology, and peptide/protein chemistry. One of his notable contributions is in the field of cyclotides, which are small, cyclic peptides with remarkable stability and diverse biological activities. Cyclotides are small, disulfide-rich peptides that have a stable cyclic backbone, making them highly resistant to enzymatic degradation. They have potential applications in drug design and development due to their stability and ability to bind to specific targets for the development of targeted therapies. Dr. Camarero’s work has significantly advanced the understanding and application of cyclotides, making them a promising area of research in peptide-based drug discovery.

Key Contributions of Dr. Camarero to Cyclotide Research:
1. Chemical Synthesis of Cyclotides:
• Camarero has developed methods for the chemical synthesis of cyclotides, enabling the production of these peptides in the lab. This includes using native chemical ligation (NCL) and other peptide synthesis techniques to create cyclotides with specific modifications.

2. Engineering Cyclotides for Drug Design:
• His work has focused on modifying cyclotides to enhance their therapeutic potential. Cyclotides have been engineered to target specific proteins or pathways, making them promising candidates for drug development. This includes modifying cyclotides to improve their therapeutic potential against cancer and infectious diseases.

3. Understanding Cyclotide Folding and Stability:
• Dr. Camarero has studied the unique structural features of cyclotides, such as their cyclic backbone and disulfide bonds, which contribute to their exceptional stability. This research has provided insights into how cyclotides can be used in biomedical applications.

4. Applications in Biotechnology and Medicine:
• His research has explored the use of cyclotides in various applications, including as antimicrobial agents (specifically against multidrug-resistant bacterial pathogens), anticancer-targeted therapeutics (CXCR4, p53, and RAS/RAF pathways), and drug delivery systems primarily to access the Central Nervous System (CNS).

Education and Training

  • University of Barcelona, Barcelona (Spain) — M.Sc. — 1992 — Chemical Biology
  • University of Barcelona, Barcelona (Spain) — Ph.D. — 1995 — Chemical Biology
  • The Rockefeller University, New York (NY) — Posdoc — 2000 — Chemical Biology
  • Lawrence Livermore National Laboratory, Livermore (CA) — Lawrence Fellow — 2003 — Chemical Biology and Bioorganic Chemistry

Research Funding

  • Therapeutic Targeting of the Hdm2/HdmX E3 Ligase in Colorectal Cancer
    American Cancer Society (ACS) · Jan 1, 2024 – Dec 31, 2025 · Role: PI
  • Therapeutic targeting of Hdm2/HdmX E3 ligase in melanoma. MRA Established Investigator Award
    Melanoma Research Alliance (MRA) · Jun 1, 2023 – May 31, 2026 · Role: PI
  • Therapeutic Targeting of Hdm2/HdmX E3 Ligase in Lung Carcinoma
    American Lung Association (ALA) · Jul 1, 2022 – Jun 30, 2025
  • Using the Ultrastable Cyclotide Scaffold to Modulate Protein-protein Interactions
    NIH · R35GM132072 · May 1, 2019 – Apr 30, 2025 · Role: PI
  • Therapeutic targeting of integrin a4ß7 in ulcerative colitis using ultrastable microprotein
    BROAD MEDICAL RESEARCH PROGRAM AT CCFA/INFLAMMATORY BOWEL DISEASE GRANTS · Oct 1, 2016 – Sep 1, 2018 · Role: PI
  • Development of Novel PD1/PD-L1 Antagonists Using Circular Cys-Knotted Micro Proteins
    Department of Defense office of the Congressionally Directed Medical Research Programs (CDMRP)/Lung Cancer Research Program (LCRP) · May 1, 2016 – Apr 30, 2018 · Role: PI
  • Screening and selection of specific protein-protein antagonists using ultrastable microprotein scaffolds
    NIH · R01GM113636 · Aug 1, 2015 – Apr 30, 2019 · Role: PI
  • Therapeutic selective targeting of BAFF receptors
    Lupus Research Institute (LRI) · Jan 15, 2015 – Jan 15, 2020
  • Screening and Selection of New Antagonists for the RING-Mediated Hdm2/Hdmx Interaction
    Department of Defense Office of the Congressionally Directed Medical Research Programs (CDMRP)/Prostate Cancer Research Program (PCRP) · Apr 1, 2010 – Mar 31, 2013 · Role: PI
  • Cell-based screening and selection of cyclotide-based capture reagents for protei
    NIH · R01GM090323 · Sep 30, 2009 – Aug 31, 2014 · Role: PI

Research Keywords

  • Chemical Biology
  • Protein and peptide therapeutics
  • Cancer
  • Microbial pathogenicity
  • Genetically-encoded biosensors

Publications

  • Resistance is futile: targeting multidrug-resistant bacteria with de novo Cys-rich cyclic polypeptides. RSC Chem Biol. 2023 Oct 04; 4(10):722-735.. View in PubMed
  • Lipidation of a bioactive cyclotide-based CXCR4 antagonist greatly improves its pharmacokinetic profile in vivo. J Control Release. 2023 07; 359:26-32.. View in PubMed
  • Recombinant Expression of Cyclotides Using Expressed Protein Ligation. Methods Mol Biol. 2020; 2133:327-341.. View in PubMed
  • The Potential of the Cyclotide Scaffold for Drug Development. Biomedicines. 2019 Apr 19; 7(2).. View in PubMed
  • Using backbone-cyclized Cys-rich polypeptides as molecular scaffolds to target protein-protein interactions. Biochem J. 2019 01 11; 476(1):67-83.. View in PubMed
  • Cyclotides, a versatile ultrastable micro-protein scaffold for biotechnological applications. Bioorg Med Chem Lett. 2017 12 01; 27(23):5089-5099.. View in PubMed
  • In-cell production of a genetically-encoded library based on the θ-defensin RTD-1 using a bacterial expression system. Bioorg Med Chem. 2018 03 15; 26(6):1212-1219.. View in PubMed
  • Full Sequence Amino Acid Scanning of θ-Defensin RTD-1 Yields a Potent Anthrax Lethal Factor Protease Inhibitor. J Med Chem. 2017 03 09; 60(5):1916-1927.. View in PubMed
  • Protein Chemical Modification Inside Living Cells Using Split Inteins. Methods Mol Biol. 2017; 1495:111-130.. View in PubMed
  • Recombinant Expression of Cyclotides Using Split Inteins. Methods Mol Biol. 2017; 1495:41-55.. View in PubMed