Malini Raghavan

Professor of Microbiology and Immunology, Medical School and Professor of Biophysics

malinir@umich.edu

Office Information:

6749 Med Sci II
phone: 734.647.7752

Education/Degree:

Ph.D., Princeton

About

Major Histocompatibility Complex (MHC) class I molecules are ligands for antigen receptors of CD8 T cells and Natural Killer cells. A major interest in our laboratory is in the MHC class I Antigen Processing and Presentation Pathway, the cellular pathway by which complexes of peptides and MHC class I molecules are generated and displayed on the cell surface. We study specific components of this pathway, including the transporter associated with antigen processing (TAP), tapasin, calreticulin, and ERp57.

TAP transports peptides from the cytosol to the ER for binding to class I MHC molecules, and tapasin is an ER-resident MHC class I-specific assembly factor. Our previous and ongoing work has helped define molecular mechanisms relevant to functions of TAP and tapasin. Human MHC class I genes are highly polymorphic, and polymorphism profoundly impacts the intracellular assembly. Recent genetic studies show that closely related MHC class I allotypes are associated with different rates of progression to AIDS, following HIV infection. Some of our current work is directed at understanding whether the intracellular assembly characteristics of an allotype influence the ability of the allotype to mediate a T or NK cell response.

Calreticulin plays important roles in the folding of MHC class I molecules and plant pattern recognition receptors. We are currently defining fundamental features of the biology of substrate interactions with calreticulin, and their regulation by co-chaperones and nucleotide. Although calreticulin is normally ER-resident, it is found at the cell surface in transformed, dying and stressed cells, where it functions as a pro-phagocytic ("eat-me") signal. Our current studies are focused on understanding roles for calreticulin in the phagocytic uptake of cancer cells and apoptotic cells, and molecular interactions relevant to calreticulin-dependent phagocytosis.

Research Areas(s)

Biochemical and molecular interactions underlying immune recognition events

About

Research Areas(s)

Biochemical and molecular interactions underlying immune recognition events

Highlighted Work and Publications

More Info

Glycan-dependent and -independent Interactions Contribute to Cellular Substrate Recruitment by Calreticulin

S.J. Wijeyesakere, S.M. Rizvi, M. Raghavan

Name of Periodical: J Biol Chem

Volume Number: 288

Issue Number: 49

Year of Publication: 2013

Page Numbers: 35104-35116

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Analyses of Conformational States of the Transporter Associated with Antigen Processing (TAP) Protein in a Native Cellular Membrane Environment.

J. Geng, S. Sivaramakrishnan, M. Raghavan

Name of Periodical: J Biol Chem

Volume Number: 288

Issue Number: 52

Year of Publication: 2013

Page Numbers: 37039-37047

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Calreticulin in the Immune System: Ins and Outs

M. Raghavan, S.J. Wijeyesakere, L.R. Peters, N. Del Cid

Name of Periodical: Trends Immunol

Volume Number: 34

Issue Number: 1

Year of Publication: 2013

Page Numbers: 13-21

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Assessment of Roles for Calreticulin in the Cross-Presentation of Soluble and Bead-Associated Antigens

N. Del Cid, L. Shen, J. Belleisle, M. Raghavan

Name of Periodical: PLoS One

Volume Number: 7

Issue Number: 7

Year of Publication: 2012

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Endoplasmic Reticulum Calcium Depletion Impacts Chaperone Secretion, Innate Immunity, and Phagocytic Uptake of Cells

L.R. Peters, M. Raghavan

Name of Periodical: J Immunol

Volume Number: 187

Issue Number: 2

Year of Publication: 2011

Page Numbers: 919-931

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Calreticulin is a Thermostable Protein with Distinct Structural Responses to Different Divalent Cation Environments

S.J. Wijeyesakere, A.A. Gafni, M. Raghavan

Name of Periodical: J Biol Chem

Volume Number: 286

Issue Number: 11

Year of Publication: 2011

Page Numbers: 8771-8785

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Distinct Functions for the Glycans of Tapasin and Heavy Chains in the Assembly of MHC Class I Molecules

S.M. Rizvi, N. Del Cid, L. Lybarger, M. Raghavan

Name of Periodical: J Immunol

Volume Number: 186

Issue Number: 4

Year of Publication: 2011

Page Numbers: 2309-2320

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The Polypeptide Binding Conformation of Calreticulin Facilitates Its Cell-surface Expression Under Conditions of Endoplasmic Reticulum Stress

E. Jeffery, L.R. Peters, M. Raghavan

Name of Periodical: J Biol Chem

Volume Number: 286

Issue Number: 4

Year of Publication: 2011

Page Numbers: 2402-2415

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Structure and Function of Major Histocompatibility Complex Class I Antigens

X.C. Li, M. Raghavan

Name of Periodical: Curr Opin Organ Transplant

Volume Number: 15

Issue Number: 4

Year of Publication: 2010

Page Numbers: 499-504

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Mechanisms of Function of Tapasin, a Critical Major Histocompatibility Complex Class I Assembly Factor

S.M. Rizvi, M. Raghavan

Name of Periodical: Traffic

Volume Number: 11

Issue Number: 3

Year of Publication: 2010

Page Numbers: 332-347

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TAP-inhibitors from Old World Primate 1-herpesviruses and Their Use: WO2009008713

M. Raghavan

Name of Periodical: Expert Opin Ther Pat

Volume Number: 20

Issue Number: 2

Year of Publication: 2010

Page Numbers: 277-282

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Modes of Calreticulin Recruitment to the Major Histocompatibility Complex Class I Assembly Pathway

N. Del Cid, E. Jeffery, S.M. Rizvi, E. Stamper, L.R. Peters, W.C. Brown, C. Provoda, M. Raghavan

Name of Periodical: J Biol Chem

Volume Number: 285

Issue Number: 7

Year of Publication: 2010

Page Numbers: 4520-4535

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Assembly and Intracellular Trafficking of HLA-B3501 and HLA-B3503

V. Thammavongsa, M. Schaefer, T. Filzen, K.L. Collins, M. Carrington, N. Bangia, M. Raghavan

Name of Periodical: Immunogenetics

Volume Number: 61

Issue Number: 11-12

Year of Publication: 2009

Page Numbers: 703-716

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MHC Class I Assembly: Out and About

M. Raghavan, N. Del Cid, S.M. Rizvi, L.R. Peters

Name of Periodical: Trends Immunol

Volume Number: 29

Issue Number: 9

Year of Publication: 2008

Page Numbers: 436-443

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Catalytic Site Modifications of TAP1 and TAP2 and Their Functional Consequences

C.L. Perria, V. Rajamanickam, P.E. Lapinski, M. Raghavan

Name of Periodical: J Biol Chem

Volume Number: 281

Issue Number: 52

Year of Publication: 2006

Page Numbers: 3150-61

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Direct Peptide-Regulatable Interactions Between MHC Class I Molecules and Tapasin

S.M. Rizvi, M. Raghavan

Name of Periodical: Proc Natl Acad Sci USA

Volume Number: 103

Issue Number: 48

Year of Publication: 2006

Page Numbers: 18220-18225

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HLA-B44 Polymorphisms at Position 116 of the Heavy Chain Influence TAP Complex Binding Via an Effect on Peptide Occupancy

V. Thammavongsa, G. Raghuraman, T.M. Filzen, K.L. Collins, M. Raghavan

Name of Periodical: J Immunol

Volume Number: 177

Issue Number: 5

Year of Publication: 2006

Page Numbers: 3150-3161

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Identification of Domain Boundaries Within the N-termini of TAP1 and TAP2 and Their Importance in Tapasin Binding and Tapasin-mediated Increase in Peptide Loading of MHC Class I

E. Procko, G. Raghuraman, D.C. Wiley, M. Raghavan, R. Gaudet

Name of Periodical: Immunol Cell Biol

Volume Number: 83

Issue Number: 5

Year of Publication: 2005

Page Numbers: 475-482

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Polypeptide Substrate Recognition by Calnexin Requires Specific Conformations of the Calnexin Protein

V. Thammavongsa, L. Mancino, M. Raghavan

Name of Periodical: J Biol Chem

Volume Number: 280

Issue Number: 39

Year of Publication: 2005

Page Numbers: 33497-33505

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A Rare Transporter Associated with Antigen Processing Polymorphism Overpresented in HLAlow Colon Cancer Reveals the Functional Significance of the Signature Domain in Antigen Processing

T. Yang, P.E. Lapinski, H. Zhao, Q. Zhou, H. Zhang, M. Raghavan, Y. Liu, P. Zheng

Name of Periodical: Clin Cancer Res

Volume Number: 11

Issue Number: 10

Year of Publication: 2005

Page Numbers: 3614-3623

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A Polypeptide Binding Conformation of Calreticulin is Infuced by Heat Shock, Calcium Depletion, or by Deletion of the C-terminal Acidic Region

S.M. Rizvi, L. Mancino, V. Thammavongsa, R.L. Cantley, M. Raghavan

Name of Periodical: Mol Cell

Volume Number: 15

Issue Number: 6

Year of Publication: 2004

Page Numbers: 913-923

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A Polypeptide Binding Conformation of Calreticulin is Induced by Heat-Shock, Calcium Depletion, or by Deletion of the C-terminal Acidic Domain

S.M. Rizvi, L. Mancino, V. Thammavongsa, R.L. Cantley, M. Raghavan

Name of Periodical: Mol. Cell.

Year of Publication: 2004

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Nucleotide Interactions with Membrane-Bound Transporter Associated with Antigen Processing Proteins

P.E. Lapinski, G. Raghuraman, M. Raghavan

Name of Periodical: J Biol Chem

Volume Number: 278

Issue Number: 10

Year of Publication: 2003

Page Numbers: 8229-8237

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Nucleotide Interactions with Membrane-Bound Transporter Associated with Antigen Processing (TAP) Proteins

P.E. Lapinski, G. Raghuraman, M. Raghavan

Name of Periodical: J. Biol. Chem.

Issue Number: 278

Year of Publication: 2003

Page Numbers: 8229-8237

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Responses of Herpes Simplex Virus Type 1-infected Cells to the Presence of Extracellular Antibodies: gE-dependent Glycoprotein Capping and Enhancement in Cell-to-cell Spread

S.M. Rizvi, M. Raghavan

Name of Periodical: J Virol

Volume Number: 77

Issue Number: 1

Year of Publication: 2003

Page Numbers: 701-708

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Tapasin Interacts with the Membrane-spanning Domains of Both TAP Subunits and Enhances the Structural Stability of TAP1 x TAP2 Complexes

G. Raghuraman, P.E. Lapinski, M. Raghavan

Name of Periodical: J Biol Chem

Volume Number: 277

Issue Number: 44

Year of Publication: 2002

Page Numbers: 41786-41794

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Calreticulin Recognizes Misfolded HLA-A2 Heavy Chains

L. Mancino, S.M. Rizvi, P.E. Lapinski, M. Raghavan

Name of Periodical: Proc. Natl. Acad. Sci.

Issue Number: 99

Year of Publication: 2002

Page Numbers: 5931-5936

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Tapasin Interacts with the Membrane Spanning Domains of Both TAP Subunits and Enhances the Structural Stability of TAP1/TAP2 Complexes

G. Raghuraman, P.E. Lapinski, M. Raghavan

Name of Periodical: J. Biol. Chem.

Issue Number: 277

Year of Publication: 2002

Page Numbers: 41786-41794

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The Use of Chimeric Proteins to Investigate the Role of Transporter Associated with Antigen Processing Structural Domains in Peptide Binding and Translocation

S.A. Arora, P.E. Lapinski, Raghavan, M.

Name of Periodical: Proc. Natl. Acad.

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Malini Raghavan

About

Research Areas(s)

About

Research Areas(s)

Highlighted Work and Publications

Glycan-dependent and -independent Interactions Contribute to Cellular Substrate Recruitment by Calreticulin

Analyses of Conformational States of the Transporter Associated with Antigen Processing (TAP) Protein in a Native Cellular Membrane Environment.

Calreticulin in the Immune System: Ins and Outs

Assessment of Roles for Calreticulin in the Cross-Presentation of Soluble and Bead-Associated Antigens

Endoplasmic Reticulum Calcium Depletion Impacts Chaperone Secretion, Innate Immunity, and Phagocytic Uptake of Cells

Calreticulin is a Thermostable Protein with Distinct Structural Responses to Different Divalent Cation Environments

Distinct Functions for the Glycans of Tapasin and Heavy Chains in the Assembly of MHC Class I Molecules

The Polypeptide Binding Conformation of Calreticulin Facilitates Its Cell-surface Expression Under Conditions of Endoplasmic Reticulum Stress

Structure and Function of Major Histocompatibility Complex Class I Antigens

Mechanisms of Function of Tapasin, a Critical Major Histocompatibility Complex Class I Assembly Factor

TAP-inhibitors from Old World Primate 1-herpesviruses and Their Use: WO2009008713

Modes of Calreticulin Recruitment to the Major Histocompatibility Complex Class I Assembly Pathway

Assembly and Intracellular Trafficking of HLA-B3501 and HLA-B3503

MHC Class I Assembly: Out and About

Catalytic Site Modifications of TAP1 and TAP2 and Their Functional Consequences

Direct Peptide-Regulatable Interactions Between MHC Class I Molecules and Tapasin

HLA-B44 Polymorphisms at Position 116 of the Heavy Chain Influence TAP Complex Binding Via an Effect on Peptide Occupancy

Identification of Domain Boundaries Within the N-termini of TAP1 and TAP2 and Their Importance in Tapasin Binding and Tapasin-mediated Increase in Peptide Loading of MHC Class I

Polypeptide Substrate Recognition by Calnexin Requires Specific Conformations of the Calnexin Protein

A Rare Transporter Associated with Antigen Processing Polymorphism Overpresented in HLAlow Colon Cancer Reveals the Functional Significance of the Signature Domain in Antigen Processing

A Polypeptide Binding Conformation of Calreticulin is Infuced by Heat Shock, Calcium Depletion, or by Deletion of the C-terminal Acidic Region

A Polypeptide Binding Conformation of Calreticulin is Induced by Heat-Shock, Calcium Depletion, or by Deletion of the C-terminal Acidic Domain

Nucleotide Interactions with Membrane-Bound Transporter Associated with Antigen Processing Proteins

Nucleotide Interactions with Membrane-Bound Transporter Associated with Antigen Processing (TAP) Proteins

Responses of Herpes Simplex Virus Type 1-infected Cells to the Presence of Extracellular Antibodies: gE-dependent Glycoprotein Capping and Enhancement in Cell-to-cell Spread

Tapasin Interacts with the Membrane-spanning Domains of Both TAP Subunits and Enhances the Structural Stability of TAP1 x TAP2 Complexes

Calreticulin Recognizes Misfolded HLA-A2 Heavy Chains

Tapasin Interacts with the Membrane Spanning Domains of Both TAP Subunits and Enhances the Structural Stability of TAP1/TAP2 Complexes

The Use of Chimeric Proteins to Investigate the Role of Transporter Associated with Antigen Processing Structural Domains in Peptide Binding and Translocation

Search: {{$root.lsaSearchQuery.q}}, Page {{$root.page}}

for

Search: {{$root.lsaSearchQuery.q}}, Page {{$root.page}}

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Malini Raghavan

About

Research Areas(s)

About

Research Areas(s)

Highlighted Work and Publications

Glycan-dependent and -independent Interactions Contribute to Cellular Substrate Recruitment by Calreticulin

Analyses of Conformational States of the Transporter Associated with Antigen Processing (TAP) Protein in a Native Cellular Membrane Environment.

Calreticulin in the Immune System: Ins and Outs

Assessment of Roles for Calreticulin in the Cross-Presentation of Soluble and Bead-Associated Antigens

Endoplasmic Reticulum Calcium Depletion Impacts Chaperone Secretion, Innate Immunity, and Phagocytic Uptake of Cells

Calreticulin is a Thermostable Protein with Distinct Structural Responses to Different Divalent Cation Environments

Distinct Functions for the Glycans of Tapasin and Heavy Chains in the Assembly of MHC Class I Molecules

The Polypeptide Binding Conformation of Calreticulin Facilitates Its Cell-surface Expression Under Conditions of Endoplasmic Reticulum Stress

Structure and Function of Major Histocompatibility Complex Class I Antigens

Mechanisms of Function of Tapasin, a Critical Major Histocompatibility Complex Class I Assembly Factor

TAP-inhibitors from Old World Primate 1-herpesviruses and Their Use: WO2009008713

Modes of Calreticulin Recruitment to the Major Histocompatibility Complex Class I Assembly Pathway

Assembly and Intracellular Trafficking of HLA-B*3501 and HLA-B*3503

MHC Class I Assembly: Out and About

Catalytic Site Modifications of TAP1 and TAP2 and Their Functional Consequences

Direct Peptide-Regulatable Interactions Between MHC Class I Molecules and Tapasin

HLA-B44 Polymorphisms at Position 116 of the Heavy Chain Influence TAP Complex Binding Via an Effect on Peptide Occupancy

Identification of Domain Boundaries Within the N-termini of TAP1 and TAP2 and Their Importance in Tapasin Binding and Tapasin-mediated Increase in Peptide Loading of MHC Class I

Polypeptide Substrate Recognition by Calnexin Requires Specific Conformations of the Calnexin Protein

A Rare Transporter Associated with Antigen Processing Polymorphism Overpresented in HLAlow Colon Cancer Reveals the Functional Significance of the Signature Domain in Antigen Processing

A Polypeptide Binding Conformation of Calreticulin is Infuced by Heat Shock, Calcium Depletion, or by Deletion of the C-terminal Acidic Region

A Polypeptide Binding Conformation of Calreticulin is Induced by Heat-Shock, Calcium Depletion, or by Deletion of the C-terminal Acidic Domain

Nucleotide Interactions with Membrane-Bound Transporter Associated with Antigen Processing Proteins

Nucleotide Interactions with Membrane-Bound Transporter Associated with Antigen Processing (TAP) Proteins

Responses of Herpes Simplex Virus Type 1-infected Cells to the Presence of Extracellular Antibodies: gE-dependent Glycoprotein Capping and Enhancement in Cell-to-cell Spread

Tapasin Interacts with the Membrane-spanning Domains of Both TAP Subunits and Enhances the Structural Stability of TAP1 x TAP2 Complexes

Calreticulin Recognizes Misfolded HLA-A2 Heavy Chains

Tapasin Interacts with the Membrane Spanning Domains of Both TAP Subunits and Enhances the Structural Stability of TAP1/TAP2 Complexes

The Use of Chimeric Proteins to Investigate the Role of Transporter Associated with Antigen Processing Structural Domains in Peptide Binding and Translocation

Assembly and Intracellular Trafficking of HLA-B3501 and HLA-B3503