Principal Investigator

Dr. Deborah Schechtman
Deborah Schechtman (IQ-USP)
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Deborah Schechtman, obtained her BA in Biological Sciences (Biomedidine) from the Universidade Federal do Estado do Rio de Janeiro (Uni-Rio), masters in Biological Siences  Biológicas (Biophysics) from the Universidade Federal do Rio de Janeiro, and PhD in the department of Chemical Immunology at The  Weizmann Institute of Science. Accomplished her Post doctoral studies at the  University of Stanford. Was a Young Investigator (FAPESP) at the Heart Institute  (InCor/ HCFMUSP) at the Laboratory  of Genetics and Molecular Cardiology.  Presently is an associate  Professor  at the Chemistry  Instituto Biochemistry Department of the Universidade de São Paulo, working on signal transduction pathways leading to pain.

The Laboratory of  Biochemistry of Cell  Signaling is localized at LAPIC, Chemistry Institute of the University of São Paulo and has as a main goal  understand the signal transduction pathways involved in pain for the development of new non-opioid analgesics.

Analyzing mutations in TrkA the  tyrosine kinase coupled e high affinity NGF receptor, in patients with congenital insensitivity to pain with anhidrosis (CIPA), and thus these patients don't feel pain, we identified the PLCg pathway activated by  TrkA as a key pathway for pain signaling.  We developed a peptide that inhibits this signaling pathway. This peptide has an analgesic effect in animal models of inflammatory pain. Using multidisciplinary approaches that involve  structural biology, physiology, embryology, biochemistry, chemistry and  cell biology and  several collaborators in Brazil and world wide  we are looking at the effects of this peptide in other animal pain models, understanding how mutations in TrkA can affect the development of the peripheral nociceptive nervous system and identifying other signaling pathways that may be affected by the peptide, and characterizing the effect of this pathway in pain. We are also developing strategies to find small molecules that can act like the peptide and can serve as leads to develop new analgesics.

We are a laboratory that values diversity, working together to achieve our goals.
We have opportunities for  undergraduate and graduate students as well as  post-docs to join us Este endereço de email está sendo protegido de spambots. Você precisa do JavaScript ativado para vê-lo.




 

People 

Postdocs

 
The effect  of mutations of the gene NTRK1 found in patients with Congenital Insensitivity to pain in the  nociceptive nervous system.

Develop a system to study the effects of mutations on the gene  NTRK1 que that leads to congenital insensitivity to pain with anhidrosis (CIPA) in the development of nocicepors  in chicken embryos.

Dr. Felipe Monteleone Vieceli
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PhD Students


Searching for small molecules that interfere with the TrkA/ PLCγ  interation

Our group establishmed that the  protein/ protein interaction between TrkA and PLCγ is a target for new analgesics, making it  important to study the specificity of PLCγ 's SH2 domains in the recognition of TrkA. Besides studying the specificity of  PLCγ 's SH2 domains for diverse peptides derived from growth factor receptor coupled tyrosine kinases  we search for new strategies to find modulators for this interaction.  In a fragment library screening assay we found  algumas candidate molecules to be  validated both structurally and functionally. We can chemically improve these molecules to test them in biochemical and in vivo assays.

Msc. Allan Pradelli Roldão
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The role of PLC
g in experimental acute and chronic pain induced hypersensitivity

Recently our lab developed a peptide, TAT-pQYP, that acts by inibiting the  PLCg pathway via  TrkA and that has an analgesic effect in acute inflammatory pain in animals. Continuing the project developed during my masters, my PhD's project goal is to characterize the effect of the inhibition of specific  signaling pathways activated by  TrkA in chronic pain models, mainly the role of PLCg in the development of chronic pain in animals, using beahvioural assays  biochemical and molecular biology techniques to elucidate the role of  the modulation of these pathways and the interaction between pathways, in this complex disease model affecting millions of people worldwide. 


Msc. Beatriz C. de Moraes
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Masters Students


Effect of the interaction between TrkA and PLCg in peripheral hypersensitivity signaling mediated by TRPV1 


Understanding how nococeptive signaling occurrs is fundamental for the development of new analgesics, necessary considering the low efficiency of the available opioids.  The objective of my project is to evaluate  d PLCγ dependent and independent mechanisms for peripheral sensitization mediated by TRPV1, besides it's role in the associated inflammation. Using a variaty  of inflammatory hipersensitivity models evaluating behaviour as a main strategy  to investigate the role of signaling pathways in analogous pain phenotypes. Furthermore, human and mice transcriptome data available and tools to modulate  specific  proteín/ proteín interactions are used to elucidate the role of e PLCγ in nociceptive signaling pathways
 
Alexandre Martins do Nascimento
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Undergraduate Students




Identification of proteins that bind to TAT-pQYP

My project aims to find proteins that bind to the peptide TAT-pQYP, besides PLCg that may contribute to the analgesic effect of the peptide. To this end, we used affinity columns with the biotinilated peptide followed by  mass spectrometry, to identify binding proteins. Binding proteins are then validated as potential targets and characterized as well as the signaling pathways involved in the analgesic effect of  TAT-pQYP, and potential side effects caused by the peptide.

Heloisa Espreáfico Guelerman Ramos 
Heloisa Ramos
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Characterization of the  peptide derived from the anchoring site  of PI3K on   TrkA and its effect on sigal transduction pattways.

My project we will perform an in depth analysis of the  PI3K and PLCg  sigaling pathways that are implicated in pain signaling.  Therefore, we wish to test cell permeable phosphopeptides  capable of biding to their respective domains in these pathways  inducing modulatios that will permit to better describe their role in cell processess. such as neurite outgrowth, and interaction with other proteins related to TrkA. To this end we will develop a cell line usig Neuro2A cells, that overexpresses TrkA. This cell line will also help us test the function of small molecule modulators of TrkA-PLCg interactions as described above.

Giovanna Souza Stival 
Giovanna Stival
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Technicians

  As a Lab Manager, I assist undergraduate and graduate students in conducting their experiments.
My work involves practical guidance, problem-solving, and teaching essential experimental techniques. I also plan and organize some of the experiments conducted in the laboratory, ensuring that all steps are followed correctly and that the results are accurate and reproducible. Additionally, I am involved in an innovative project focused on the implementation of new drugs for pain treatment. This project not only expands our scientific knowledge but also has the potential to positively impact patients' quality of life. Overall, my role is to ensure that the laboratory operates smoothly and efficiently, facilitating high-quality research and contributing to scientific advancement in our field.  

Dr. Ana Maria Rodrigues 
Lab Manager
Ana Maria Rodrigues
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Some publications from our group  

   
Expression and Function of PKMz in Development

- Pramio DT, Vieceli FM, Varella-Branco E, Goes CP, Kobayashi GS, Pelegrina DVS, Moraes BC, El Allam A, Kumar BD, Jara G, Farfel JM, Bennett DA, Kundu S, Viapiano MS, Reis EM, Oliveira PSL, Passos-Bueno MRS, Rothlin CV, Ghosh S, Schechtman D (2023)DNA methylation of the promoter region at the CREB1 binding site is a mechanism for the epigenetic regulation of brain-specific PKMζ. Biochim. Biophys. Acta - Gene Regul. Mech. v.1866, p.194909.

In the News
Folha.uol.com.br/ciencia/2023/08/
Agencia.fapesp.

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 Ellam, E.A.; Alberto, E.J.; Mercau, M.E.; Pramio, D.T.; Bhat, K.M.; Philbrick , W.M. Schechtman, D.; Rothlin, C.V. & Ghosh, S.Functional roles of neural aPKCs in mouse brain development and survival  






 
Desenho racional de um peptídeo que inibe a via de sinalização da  PLCg ativada pela TrkA  e tem um efeito analgésico.

Moraes BC, Ribeiro-Filho HV, Roldão AP, Toniolo EF, Carretero GPB, Sgro GG, Batista FAH, Berardi DE, Oliveira VRS, Tomasin R, Vieceli FM, Pramio DT, Bruni-Cardoso A, Figueira ACM, Farah SC, Devi LA, Dale CS, De Oliveira, Paulo SL, Schechtman D (2022)Structural analysis of TrkA mutations in patients with congenital insensitivity to pain reveals PLCγ as an analgesic drug target. Science Signaling, v. 15, p. 1-15.

Notícias
DNA de pessoas insensíveis à dor ajuda pesquisa de nova droga no Brasil (globo.com)
Revista pesquisa.fapesp
Jornal USP
technologynetworks.com 

- Pena DA, Duarte ML, Pramio DT, Devi LA, Schechtman D (2018) Exploring Morphine-Triggered PKC-Targets and Their Interaction with Signaling Pathways Leading to Pain via TrkA. Proteomes, v. 6, p. 39

 


Generating conformational-specific antiboides that recognize specifically active  cPKCs 


- Pena DA, Andrade VP, Silva GÁ, Neves JI, Oliveira PS, Alves MJ, Devi LA & Schechtman D. Rational design and validation of an anti-protein kinase C active-state specific antibody based on conformational changes. Sci Rep. 2016 Feb 25,6:22114.

- Pena D, Pacheco DM, Oliveira PSL, Alves, MJM, Schechtman D (2018). Generating Conformation-Specific Polyclonal and Monoclonal Anti-Protein Kinase C Antibodies and Anti-Active State Specific PKC Antibodies. Current Protocols in Chemical Biology, v. 1, p. e42


- Duarte ML, Trimbake NA, Gupta A, Tumanut C, Fan X, Woods C, Ram A, Gomes I, Bobeck EN, Schechtman D, Devi LA (2021) High-throughput screening and validation of antibodies against synaptic proteins to explore opioid signaling dynamics. Communications Biology, v. 4, p. 238
 

 
Establishing the concept that kinases recognize structural consensus sites 

- Duarte ML, Pena DA, Nunes Ferraz FA, Berti DA, Paschoal Sobreira TJ, Costa-Junior HM, Abdel Baqui MM, Disatnik MH, Xavier-Neto J, Lopes de Oliveira OS & Schechtman D. Protein folding creates structure-based, noncontiguous consensus phosphorylation motifs recognized by kinases. 
Sci Signal. 2014 Nov 4,7(350):ra105. 

Notícias
Agencia.fapesp
Revista pesquisa fapesp

- Revisiting protein kinase–substrate interactions: Toward therapeutic development”
 Oliveira PS, Ferraz FAN, Pena DA, Pramio DT, Morais FA & Deborah Schechtman. Sci, Signal. 22 Mar, 2016 Re3






   
 
  Using phosphoproteomics and peptide modulators to characterize ther role of PKC isoenzymes in murine embryonic stem cells.

- Garavello NM, Pena DA, Bonatto JM, Duarte ML, Costa-Junior HM, Schumacher RI, Forti FL & Schechtman D. Activation of protein kinase C delta by ψδRACK peptide promotes embryonic stem cell proliferation through ERK 1/2. J Proteomics. 2013 Dec 6,94:497-512.

- Costa-Junior HM, Garavello NM, Duarte ML, Berti DA, Glaser T, de Andrade A, Labate CA, Ferreira AT, Perales JE, Xavier-Neto J, Krieger JE, Schechtman D. Phosphoproteomics profiling suggests a role for nuclear βΙPKC in transcription processes of undifferentiated murine embryonic stem cells. J Proteome Res. 2010 Dec 3,9(12):6191-206.
 

Videos
 
redeciencia.tv.
Estudo da Dor Abre Caminho para Novos Analgésicos (fiocruz.br)
Ciência SP (FAPESP) “Novo alvo para desenvolvimento de analgésicos”:


Alumni (Students and Post-docs)

                     
Dra. Mariana Lemos Duarte
Icahn School of Medicine at Mount Sinai, New York, USA
https://www.elahilab.com/mariana-lemos-duarte

 
 

   
Dr. José Matheus Camargo Bonatto 
Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Campinas, Brasil
   

   
Dra. Darlene A. Pena 
Profa. UNIFEBE e UNIAVAN 
   

   
Dr. Dimitrius T. Pramio 
   

   
Dr. Hélio Miranda Costa Junior
Gerente de Treinamento em Oncologia e Acesso na MSD Brasil
   

   
Dra. Denise A. Berti
Senior Researcher, Staff Scientist, UCSD em San Diego
http://msanderlab.org/denise-berti-2/
 
 

   
Dr. Damian E. Berardi
Product Scientist at Cell Signaling Technology


Msc. Nicole Milaré Garavello
Senior Clinical Research Associate na PRA Health Sciences


Dr. Felipe Alves Morais

MSc. Denise Maria Vianna Pacheco

MSc. Matheus Monteiro da Silva

Images created with Biorender.com


     
     

Department of Biochemistry
Institute of Chemistry
University of Sao Paulo - USP

Av. Prof. Lineu Prestes, 748 - office 1208
Cidade Universitaria
Cep 05508-000 - Sao Paulo - SP - Brazil

Phone: +55-11-3091-2173
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