Julio A. Camarero, PhD
John A. Biles Professor in Pharmaceutical Sciences
Pharmacology and Pharmaceutical Sciences
- Chemical biology
- Protein and peptide therapeutics
- Microbial pathogenicity
- Genetically-encoded biosensors
- (323) 442-1417
- (323) 442-1390
B.Sc. 1990 Chemistry - University of Barcelona, Spain
Ph.D. 1996 Organic Chemistry - University of Barcelona, Spain
The practical and conceptual opportunities made available by recent innovations in the emerging fields of synthetic protein chemistry and protein expression using modified protein splicing elements are providing a fertile source for innovative biotechnology tools to study the physico-chemical basis of protein function in vivo and in vitro.
The Camarero Lab is focused in using these generic chemistry-driven technologies for studying biological process involved in bacterial pathogenicity and Chem-Biosensing. Some of the actual working projects involve:
1. Development of new methods for the biosynthesis and screening of biological libraries inside living cells for the rapid detection of small molecules able to inhibit or attenuate intracellular molecular recognition events. Our initial focus has been to produce high-affinity ligands (using highly constrained circular peptides such as cyclotides as molecular scaffolds) that can disable bacterial pathogenicity and other biological toxins, but this approach can also be easily used to find small circular peptides capable of disrupting any biomolecular interaction. For example, the method can be used to find molecules that may disrupt the destructive mechanisms involved in cancer and neurodegenerative diseases such mad cow and Alzheimers.
2. Development of molecular tools for the study of protein/protein interactions in real time and at single cell level. Key to this approach is the development of new molecular tools based on photomodulated protein trans-splicing that will allow the reconstitution and site-specific labeling of particular proteins inside the host cell with total temporal and spatial control. The use and development of new orthogonal split inteins is being used for the simultaneous multicolor site-specific labeling of different proteins in vivo. This approach is being used to study the pathogenicity of Yersinia pestis (the causative agent of plague) in real time and at single cell level to better understand the virulence mechanisms associated with this human pathogen
3. Rapid production of protein microarrays to understand interactions in microbial pathogenicity and how to modulate them. This project involves interfacing the method of protein immobilization that we have developed based on protein trans-splicing with high-throughput cloning and expression methods, such as Gateway-like and cell-free expression systems. This allows the rapid production of high quality protein chips of a particular proteome. Analysis and identification of the proteins captured by the microarray is carried out using mass spectrometry (MALDI MS and MALDI MS/MS). We have started to produce protein chips containing proteins from Y. pestis type III secretion system, which include cytotoxins and effectors. This approach is being used for the analysis of protein/protein interactions to study bacterial pathogenicity.
Dr. Camarero started his studies in chemistry at the University if Barcelona (Spain), received his Master degree in 1992, and finished his PhD thesis there in 1996. Afterwards he joined the group of Professor Tom W. Muir at The 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 where he became staff scientist and head of laboratory in 2003. He joined the University of Southern California in 2007 as an associate professor, and became full professor in 2016.
His current research interests are focused in the development of new bioorganic approaches using protein splicing and synthetic protein chemistry for studying biological processes involved in human diseases, such as cancer, metabolic disorder and microbial pathogenicity, and how can be modulated or inhibited by micro-proteins, called cyclotides. Dr. Camarero has authored over 90 peer-reviewed publications and four invited book chapters.
1. Full sequence amino acid scanning of θ-defensin RTD-1 yields a potent anthrax lethal factor protease inhibitor. Li Y, Gould A, Aboye T, Bi T, Breindel LM, Shekhtman A, Camarero JA. J Med Chem. 2017; 60(5):1916-1927. PubMed -Link
4. Efficient recombinant expression of SFTI-1 in bacterial cells using intein-mediated protein trans-splicing. Li Y, Aboye T, Breindel L, Shekhtman A, Camarero JA. Biopolymers. 2016; 106(6):818-82. PubMed -Link
5. Design of a MCoTI-Based Cyclotide with Angiotensin (1-7)-Like Activity. Aboye T, Meeks CJ, Majumder S, Shekhtman A, Rodgers K, Camarero JA. Molecules. 2016 ; 21(2): 152. doi: 10.3390/molecules21020152. PubMed -Link
6. Recombinant Expression and Phenotypic Screening of a Bioactive Cyclotide Against α-Synuclein-Induced Cytotoxicity in Baker's Yeast. Jagadish K, Gould A, Borra R, Majumder S, Mushtaq Z, Shekhtman A, Camarero JA. Angew Chem Int Ed Engl. 2015 ;54(29):8390-4. PubMed -Link
7. Changing the topology of protein backbone: the effect of backbone cyclization on the structure and dynamics of a SH3 domain. Schumann FH, Varadan R, Tayakuniyil PP, Grossman JH, Camarero JA, Fushman D. Front Chem. 2015 Apr 8;3:26. doi: 10.3389/fchem.2015.00026. PubMed -Link
8. Rapid parallel synthesis of bioactive folded cyclotides by using a tea-bag approach. Aboye T, Kuang Y, Neamati N, Camarero JA. Chembiochem. 2015 Mar 23;16(5):827-33. doi: 10.1002/cbic.201402691. PubMed -Link
10. Insights into the molecular flexibility of θ-defensins by NMR relaxation analysis. Conibear AC, Wang CK, Bi T, Rosengren KJ, Camarero JA, Craik DJ. J Phys Chem B. 2014; 118(49): 14257-66. PubMed -Link
13. In vivo activation of the p53 tumor suppressor pathway by an engineered cyclotide. Ji Y, Majumder S, Millard M, Borra R, Bi T, Elnagar AY, Neamati N, Shekhtman A, Camarero JA. J Am Chem Soc. 2013; 135 (31): 11623-33. PubMed -Link
14. Expression of fluorescent cyclotides using protein trans-splicing for easy monitoring of cyclotide-protein interactions. Jagadish K, Borra R, Lacey V, Majumder S, Shekhtman A, Wang L, Camarero JA. Angew Chem Int Ed Engl. 2013; 52 (11): 3126-31. PubMed -Link
15. Design of a novel cyclotide-based CXCR4 antagonist with anti-human immunodeficiency virus (HIV)-1 activity. Aboye TL, Ha H, Majumder S, Christ F, Debyser Z, Shekhtman A, Neamati N, Camarero JA. J Med Chem. 2012 ; 55 (23): 10729-34. PubMed -Link
18. In-cell fluorescence activation and labeling of proteins mediated by FRET-quenched split inteins. Borra R, Dong D, Elnagar AY, Woldemariam GA, Camarero JA. J Am Chem Soc. 2012 ; 134 (14): 6344-53. PubMed -Link
19. Recombinant production of rhesus θ-defensin-1 (RTD-1) using a bacterial expression system. Gould A, Li Y, Majumder S, Garcia AE, Carlsson P, Shekhtman A, Camarero JA. Mol Biosyst. 2012 ; 8 (4): 1359-65. PubMed -Link
20. Biosynthesis and antimicrobial evaluation of backbone-cyclized α-defensins. Garcia AE, Tai KP, Puttamadappa SS, Shekhtman A, Ouellette AJ, Camarero JA. Biochemistry. 2011; 50 (48): 10508-19. PubMed -Link
24. Biological activities of natural and engineered cyclotides, a novel molecular scaffold for peptide-based therapeutics. Garcia AE, Camarero JA. Curr Mol Pharmacol. 2010; 3 (3): 153-63. PubMed -Link
28. Biosynthesis and biological screening of a genetically encoded library based on the cyclotide MCoTI-I. Austin J, Wang W, Puttamadappa S, Shekhtman A, Camarero JA. Chembiochem. 2009; 10 (16): 2663-70. PubMed -Link