Department of Pathology

Department Faculty

Dr. Cristina C. Clement, Ph.D.

Cristina C. Clement, Ph.D.

Research Assistant Professor, Department of Pathology

Professional Interests

I am currently Research Assistant Professor assigned to the Pathology Department of the Albert Einstein College of Medicine (AECM). I have a long and well-documented track record of accomplished and productive research projects in the field of mass spectrometry applied to “omics”, particularly the peptidomics/proteomics and lipidomics profiling of many biological systems.  My technical expertise is owing to many years of specific training and hands-on experience received while conducting a wide range of research in biochemistry, bioorganic chemistry, molecular pharmacology and proteomics/peptidomics analysis. As a postdoctoral fellow at Sloan Kettering Institute (NY) I conducted research focusing on the discovery of new inhibitors of Hsp-70 and Hsp-90 and their roles in anti-cancer treatment by using computational tools, biophysics, and cell-based assays.   As a postdoctoral research associate at AECOM I expanded my research to include the development and optimization of mass spectrometric (MS) based assays, specifically, 1DEF nanoLC Orbitrap-ESI-MS/MS and two-dimensional fluorescence difference-in-gel electrophoresis (2D-DIGE nanoLC-ESI-MS/MS.   The MS assays I developed covered global and targeted peptidomics, lipidomics, and proteomics analysis of many biological fluids, including human lymph, plasma, synovial fluid. These MS assays also covered different cells systems, including human dendritic cells and cartilage, among others, while making valuable use of both qualitative and label-free quantitative (LFQ) tools.  As a Research Assistant Professor who was named on several university and NIH-funded grants awarded to my AECOM PI, Dr. Laura Santambrogio, I helped lay the groundwork for the many research projects by developing effective redox proteomics assays that were coupled with high-throughput analysis of post-translational modifications aimed at revealing the molecular mechanisms related to the effects of “oxidative stress” in aging.

In addition, I have successfully administered each of these projects, overseeing the staffing, the research training of postdoctoral fellows and students, and collaboration with other researchers. These efforts have resulted in several peer-reviewed publications.

Research conducted in the lab of Dr. Laura Santambrogio in the Pathology Department/AECOM.

1. Mass spectrometry of proteins and peptides from different biological fluids (lymph, plasma, synovial fluid), biomarkers discovery;  label and label free quantitative proteomics aproaches for monitoring redox changes in the proteomes during aging and autoimmune diseases/cancer. 

2. Enzyme based peptidomics coupled with nanoLC/MS/MS for discovery of neoepitopes derived from the processing of extracellular proteins.

3. PTM (posttranslational modification) scanning and Redox proteomics (PTM of oxidative stress) assays for profiling of peptides/proteins in dendritic and other immune cells in aging, autoimmune diseases and immuno-compromised pathological states.

4. Biophysical methods for study the proteins folding/unfolding under oxidative stress (oxygen free radical modified proteins): circular dichroism for secondary structural changes during oxidation of collagens, fluorescence studies of the tertiary structures changes during proteins unfolding under pathological conditions (such as reactive oxygen species generated during oxidative stress in aging).

5. SBDD (structure-based drug design) coupled with HTS in silico virtual screening of chemical and drug-like libraries for discovery of inhbitors for Hsc70/Hsp-70; coagulation factors (thrombin, Factor VIIa/TF, factor XI and factor XII). I use molecular docking approaches which employ software for drug design and discovery, such as Autodock Vina (Scripps Institute), MOE (CCG) and SMALL-MOLECULE DRUG DISCOVERY SUITE from Schrodinger.

Selected Publications

1) In the laboratory of Dr. Laura Santmabrogio I developed the proteomic and peptidomics assays coupled with advanced bioinformatics analysis of the molecular and cellular pathways for analysis of the human lymph and characterization its self-antigen peptide repertoire available for MHC II presentation.  The global proteomics/peptidomics analysis was coupled with the development of cell-free systems, including isolated organelles such as late endosomes, plasma membrane, and cytosol, as well as enzymatic-based assays aimed to characterize the differential antigen-processing pathways that generate the peptidome of the human lymph.

Clement CC, Becerra A, Yin L, Zolla V, Merlin S, Follenzi A, Shafer S, Stern L, Santambrogio L. The dendritic cell MHC II peptidome derives from a variety of processing pathways and includes peptides with a broad spectrum of HLA-DM sensitivity. J Biol Chem. 2016 Jan 6. pii: jbc.M115.655738. [Epub ahead of print] PMID: 26740625

Clement CC, Aphkhazava D, Nieves E, Callaway M, Olszewski W, Rotzschke O, Santambrogio L.  Protein expression profiles of human lymph and plasma mapped by 2D-DIGE and 1D SDS-PAGE coupled with nanoLC-ESI-MS/MS bottom-up proteomics. J Proteomics2013 Jan 14;78:172-87. doi: 10.1016/j.jprot.2012.11.013.

C.C. Clement, O. Rotzschke, L. Santambrogio. The Lymph as a pool of self-antigens. Trends in Immunology. 2011;32(1):6-11. PMID: 21123113

C.C. Clement, E.S. Cannizzo, M. Nastke, R. Sahu, W. Olszewski, N.E. Miller, L.J. Stern, L. Santambrogio. An Expanded self-antigen peptidome is carried      by the human lymph as compared to the plasma. PLoS ONE. 2010 Mar 26;5(3):e9863. doi: 10.1371/journal.pone.0009863.

 

2) In the lab of Dr. Laura Santambrogio I developed and optimized the redox proteomics and lipidomics assays coupled with high-throughput analysis of post-translational modifications capable of revealing the molecular mechanisms related to the effects of “oxidative stress” in aging, and other proinflammatory situations.

 

Tanase M, Urbanska A, Zolla V, Clement CC, Morozova K, Roda B, Reschiglian P, Santambrogio L. Role of Carbonyl Modifications on Aging-Associated Protein Aggregation. Scientific Reports 2016 Jan 18;6:19311 doi: 10.1038/srep19311. PMID:26776680.

E. S. Cannizzo, C. C. Clement,K. Morozova, R. Valdor,  S. Kaushik, L. Almeida, C. Follo, A.M. Cuervo, F. J. Macian, L. Santambrogio. (2012) Age-related Oxidative Stress Compromises Endosomal Proteostasis. Cell Reports 2012 Jul 26;2(1):136-49. doi: 10.1016/j.celrep.2012.06.005.

Tanase M, Zolla V, Clement CC, Borghi F, Urbanska A,  Rodriguez-Navarro JA, Roda B, Zattoni A, Reschiglian P, Cuervo AM, Santambrogio L. Hydrodynamic-size based separation and characterization of protein aggregates from total cell lysates. Nature Protocols 2015 Jan;10(1):134-48. doi: 10.1038/nprot.2015.009.

E. S. Cannizzo, C.C. Clement, R. Sahu, C.  Follo, L. Santambrogio. Oxidative stress, Inflamm-aging and Immunosenescence. J. Proteomic. 2011, Oct 19;74 (11):2313-23. doi: 10.1016/j.jprot.2011.06.005.

Scharf B, Clement CC, Yodmuang S, Urbanska AM, Suadicani SO, Aphkhazava D, Thi MM, Perino G, Hardin JA, Cobelli N, Vunjak-Novakovic G, Santambrogio L.  Age-related carbonylation of fibrocartilage structural proteins drives tissue degenerative modification.  Chem Biol. 2013 Jul 25; 20(7):922-34.

Scharf B, Clement CC, Wu XX, Morozova K, Zanolini D, Follenzi A, Larocca JN, Levon K, Sutterwala FS, Rand J, Cobelli N, Purdue E, Hajjar KA, Santambrogio L.  Annexin A2 binds to endosomes following organelle destabilization by particulate wear debris. Nat Commun. 2012 Mar 27; 3:755. doi: 10.1038/ncomms1754.

Scharf B, Clement CC, Zolla V, Perino G, Yan B, Elci SG, Purdue E, Goldring S, Macaluso F, Cobelli N, Vachet RW, Santambrogio L.  Molecular analysis of chromium and cobalt-related toxicity.  Sci Rep. 2014 Jul 17; 4:5729.

Zolla V, Nizamutdinova IT, Scharf B, Clement CC, Maejima D, Akl T, Nagai T, Luciani P, Leroux JC, Halin C, Stukes S, Tiwari S, Casadevall A, Jacobs WR Jr, Entenberg D, Zawieja DC, Condeelis J, Fooksman DR, Gashev AA, Santambrogio L.  Aging-related anatomical and biochemical changes in lymphatic collectors impair lymph transport, fluid homeostasis, and pathogen clearance.  Aging Cell. 2015 Aug; 14(4):582-94. doi: 10.1111/acel.12330.

Morozova K, Sidhar S, Zolla V, Clement CC, Scharf B, Verzani Z, Diaz A, Larocca JN, Hajjar KA, Cuervo AM, Santambrogio L.  Annexin A2 promotes phagophore assembly by enhancing Atg16L⁺ vesicle biogenesis and homotypic fusion. Nat Commun. 2015 Jan 19; 6:5856.

 3) In the lab of Dr. Laura Santambrogio I developed and optimized the peptidomics/proteomics assays aimed to discover the neopeptides epitopes, potential biomarkers of juvenile idiopathic arthritis (JIA).  These assays, followed further by immunological functional validations, highlighted transthyretin as a biomarker   of JIA disease.

Clement CC, Moncriefe H, Lele A, Janow G, Becerra A, Bauli F, Saad FA, Perino G, Montagna C, Cobelli N, Hardin J, Stern LJ, Ilowite N, Porcelli SA, Santambrogio L. Autoimmune response to transthyretin in juvenile idiopathic arthritis.  JCI Insight. 2016 Feb; 1(2). pii: e85633. Epub 2016 Feb 25.

Other research performed at Albert Einstein College of Medicine (2007-present) 

1: Morozova K, Clement CC, Kaushik S, Stiller B, Arias E, Ahmad A, Rauch JN, Chatterjee V, Melis C, Scharf B, Gestwicki JE, Cuervo AM, Zuiderweg ER, Santambrogio L. Structural and Biological Interaction of hsc-70 Protein with Phosphatidylserine in Endosomal Microautophagy. J Biol Chem. 2016 Aug 26;291(35):18096-106. doi: 10.1074/jbc.M116.736744. Epub 2016 Jul 12. PubMed PMID: 27405763; PubMed Central PMCID: PMC5000059. 

2: Hansen KC, D'Alessandro A, Clement CC, Santambrogio L. Lymph formation, composition and circulation: a proteomics perspective. Int Immunol. 2015 May;27(5):219-27. doi: 10.1093/intimm/dxv012. Epub 2015 Mar 18. Review. PubMed PMID: 25788586.

3: Clement CC, Santambrogio L. The lymph self-antigen repertoire. Front Immunol. 2013 Dec 16;4:424. doi: 10.3389/fimmu.2013.00424. Review. PubMed PMID: 24379811; PubMed Central PMCID: PMC3864156.

 4: Sahu R, Kaushik S, Clement CC, Cannizzo ES, Scharf B, Follenzi A, Potolicchio I, Nieves E, Cuervo AM, Santambrogio L. Microautophagy of cytosolic proteins by late endosomes. Dev Cell. 2011 Jan 18;20(1):131-9. doi: 10.1016/j.devcel.2010.12.003. Erratum in: Dev Cell. 2011 Mar 15;20(3):405-6. PubMed PMID: 21238931; PubMed Central PMCID: PMC3025279.

 5: Maitra R, Clement CC, Scharf B, Crisi GM, Chitta S, Paget D, Purdue PE, Cobelli N, Santambrogio L. Endosomal damage and TLR2 mediated inflammasome activation by alkane particles in the generation of aseptic osteolysis. Mol Immunol. 2009 Dec;47(2-3):175-84. doi: 10.1016/j.molimm.2009.09.023. Epub 2009 Oct 4. PubMed PMID: 19804908; PubMed Central PMCID: PMC2787895.

 Shared first authorship with Maitra R

 6: Maitra R, Clement CC, Crisi GM, Cobelli N, Santambrogio L. Immunogenecity of  modified alkane polymers is mediated through TLR1/2 activation. PLoS One. 2008 Jun 18;3(6):e2438. doi: 10.1371/journal.pone.0002438. PubMed PMID: 18560588; PubMed Central PMCID: PMC2413007.

 

 

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