Albert C Shaw, MD, PhD
Research & Publications
Biography
News
Research Summary
Research in the Shaw laboratory is directed toward understanding the mechanisms underlying the functional decline of the human immune system with aging. Our group demonstrated age-associated alterations in human Toll-like receptor function, and remains engaged in understanding the function of these and other innate immune pattern recognition receptors (PRRs) in older adults--particularly the contribution of such PRRs to the heightened pro-inflammatory milieu found in older adults (so-called "Inflamm-Aging"). We are particularly interested in the effects of age on immunologic, gene expression and metabolic signatures of influenza vaccine response, in view of the particularly poor responses to vaccination found in older adults and the need for improved influenza vaccines. Additional ongoing projects include the study of immune system aging in the context of HIV infection (with older adults constituting one of the fastest growing groups with HIV disease) and of the differential effects of agents used for medication-assisted therapy of opioid use disorders (such as methadone and buprenorphine) on immunologic responses and inflammation in individuals with and without HIV infection.
Specialized Terms: Mechanisms underlying the functional decline of the immune system with aging
Coauthors
Research Interests
Aging; DNA Repair; Immune System; Immunity, Innate; Influenza Vaccines; Toll-Like Receptors; Infectious Disease Medicine
Selected Publications
- Design and implementation of a prospective cohort study of persons living with and without HIV infection who are initiating medication treatment for opioid use disorder.Biondi BE, Mohanty S, Wyk BV, Montgomery RR, Shaw AC, Springer SA. Design and implementation of a prospective cohort study of persons living with and without HIV infection who are initiating medication treatment for opioid use disorder. Contemporary Clinical Trials Communications 2021, 21: 100704. PMID: 33490708, PMCID: PMC7807244, DOI: 10.1016/j.conctc.2021.100704.
- Seasonal Variability and Shared Molecular Signatures of Inactivated Influenza Vaccination in Young and Older Adults.Avey S, Mohanty S, Chawla DG, Meng H, Bandaranayake T, Ueda I, Zapata HJ, Park K, Blevins TP, Tsang S, Belshe RB, Kaech SM, Shaw AC, Kleinstein SH. Seasonal Variability and Shared Molecular Signatures of Inactivated Influenza Vaccination in Young and Older Adults. Journal Of Immunology (Baltimore, Md. : 1950) 2020, 204: 1661-1673. PMID: 32060136, PMCID: PMC7755271, DOI: 10.4049/jimmunol.1900922.
- Longitudinal analyses reveal immunological misfiring in severe COVID-19.Lucas C, Wong P, Klein J, Castro TBR, Silva J, Sundaram M, Ellingson MK, Mao T, Oh JE, Israelow B, Takahashi T, Tokuyama M, Lu P, Venkataraman A, Park A, Mohanty S, Wang H, Wyllie AL, Vogels CBF, Earnest R, Lapidus S, Ott IM, Moore AJ, Muenker MC, Fournier JB, Campbell M, Odio CD, Casanovas-Massana A, Herbst R, Shaw AC, Medzhitov R, Schulz WL, Grubaugh ND, Dela Cruz C, Farhadian S, Ko AI, Omer SB, Iwasaki A. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature 2020, 584: 463-469. PMID: 32717743, PMCID: PMC7477538, DOI: 10.1038/s41586-020-2588-y.
- Impact of Aging and HIV Infection on the Function of the C-Type Lectin Receptor MINCLE in Monocytes.Zapata HJ, Van Ness PH, Avey S, Siconolfi B, Allore HG, Tsang S, Wilson J, Barakat L, Mohanty S, Shaw AC. Impact of Aging and HIV Infection on the Function of the C-Type Lectin Receptor MINCLE in Monocytes. The Journals Of Gerontology. Series A, Biological Sciences And Medical Sciences 2019, 74: 794-801. PMID: 30239628, PMCID: PMC6521921, DOI: 10.1093/gerona/gly209.
- Dissecting alterations in human CD8+ T cells with aging by high-dimensional single cell mass cytometry.Shin MS, Yim K, Moon K, Park HJ, Mohanty S, Kim JW, Montgomery RR, Shaw AC, Krishnaswamy S, Kang I. Dissecting alterations in human CD8+ T cells with aging by high-dimensional single cell mass cytometry. Clinical Immunology (Orlando, Fla.) 2019, 200: 24-30. PMID: 30659916, PMCID: PMC6443094, DOI: 10.1016/j.clim.2019.01.005.
- Aging impairs both primary and secondary RIG-I signaling for interferon induction in human monocytes.Molony RD, Nguyen JT, Kong Y, Montgomery RR, Shaw AC, Iwasaki A. Aging impairs both primary and secondary RIG-I signaling for interferon induction in human monocytes. Science Signaling 2017, 10 PMID: 29233916, PMCID: PMC6429941, DOI: 10.1126/scisignal.aan2392.
- β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares.Goldberg EL, Asher JL, Molony RD, Shaw AC, Zeiss CJ, Wang C, Morozova-Roche LA, Herzog RI, Iwasaki A, Dixit VD. β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares. Cell Reports 2017, 18: 2077-2087. PMID: 28249154, PMCID: PMC5527297, DOI: 10.1016/j.celrep.2017.02.004.
- Multiple network-constrained regressions expand insights into influenza vaccination responses.Avey S, Mohanty S, Wilson J, Zapata H, Joshi SR, Siconolfi B, Tsang S, Shaw AC, Kleinstein SH. Multiple network-constrained regressions expand insights into influenza vaccination responses. Bioinformatics (Oxford, England) 2017, 33: i208-i216. PMID: 28881994, PMCID: PMC5870750, DOI: 10.1093/bioinformatics/btx260.
- Host Resistance and Immune Aging.Bandaranayake T, Shaw AC. Host Resistance and Immune Aging. Clinics In Geriatric Medicine 2016, 32: 415-32. PMID: 27394014, PMCID: PMC6986475, DOI: 10.1016/j.cger.2016.02.007.
- Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease.Pillai PS, Molony RD, Martinod K, Dong H, Pang IK, Tal MC, Solis AG, Bielecki P, Mohanty S, Trentalange M, Homer RJ, Flavell RA, Wagner DD, Montgomery RR, Shaw AC, Staeheli P, Iwasaki A. Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease. Science (New York, N.Y.) 2016, 352: 463-6. PMID: 27102485, PMCID: PMC5465864, DOI: 10.1126/science.aaf3926.
- Prolonged proinflammatory cytokine production in monocytes modulated by interleukin 10 after influenza vaccination in older adults.Mohanty S, Joshi SR, Ueda I, Wilson J, Blevins TP, Siconolfi B, Meng H, Devine L, Raddassi K, Tsang S, Belshe RB, Hafler DA, Kaech SM, Kleinstein SH, Trentalange M, Allore HG, Shaw AC. Prolonged proinflammatory cytokine production in monocytes modulated by interleukin 10 after influenza vaccination in older adults. The Journal Of Infectious Diseases 2015, 211: 1174-84. PMID: 25367297, PMCID: PMC4366602, DOI: 10.1093/infdis/jiu573.
- Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination.Thakar J, Mohanty S, West AP, Joshi SR, Ueda I, Wilson J, Meng H, Blevins TP, Tsang S, Trentalange M, Siconolfi B, Park K, Gill TM, Belshe RB, Kaech SM, Shadel GS, Kleinstein SH, Shaw AC. Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination. Aging 2015, 7: 38-52. PMID: 25596819, PMCID: PMC4356402, DOI: 10.18632/aging.100720.
- Paradoxical changes in innate immunity in aging: recent progress and new directions.Montgomery RR, Shaw AC. Paradoxical changes in innate immunity in aging: recent progress and new directions. Journal Of Leukocyte Biology 2015, 98: 937-43. PMID: 26188078, PMCID: PMC4661037, DOI: 10.1189/jlb.5MR0315-104R.
- Aging of the human innate immune system in HIV infection.Zapata HJ, Shaw AC. Aging of the human innate immune system in HIV infection. Current Opinion In Immunology 2014, 29: 127-36. PMID: 24997358, PMCID: PMC4145838, DOI: 10.1016/j.coi.2014.06.007.
- Functional polymorphisms in the gene encoding macrophage migration inhibitory factor are associated with Gram-negative bacteremia in older adults.Das R, Subrahmanyan L, Yang IV, van Duin D, Levy R, Piecychna M, Leng L, Montgomery RR, Shaw A, Schwartz DA, Bucala R. Functional polymorphisms in the gene encoding macrophage migration inhibitory factor are associated with Gram-negative bacteremia in older adults. The Journal Of Infectious Diseases 2014, 209: 764-8. PMID: 24158957, PMCID: PMC3923543, DOI: 10.1093/infdis/jit571.
- Human monocytes have increased IFN-γ-mediated IL-15 production with age alongside altered IFN-γ receptor signaling.Lee N, Shin MS, Kang KS, Yoo SA, Mohanty S, Montgomery RR, Shaw AC, Kang I. Human monocytes have increased IFN-γ-mediated IL-15 production with age alongside altered IFN-γ receptor signaling. Clinical Immunology (Orlando, Fla.) 2014, 152: 101-10. PMID: 24657713, PMCID: PMC4018768, DOI: 10.1016/j.clim.2014.03.003.
- Chitinase 3-like 1 suppresses injury and promotes fibroproliferative responses in Mammalian lung fibrosis.Zhou Y, Peng H, Sun H, Peng X, Tang C, Gan Y, Chen X, Mathur A, Hu B, Slade MD, Montgomery RR, Shaw AC, Homer RJ, White ES, Lee CM, Moore MW, Gulati M, Lee CG, Elias JA, Herzog EL. Chitinase 3-like 1 suppresses injury and promotes fibroproliferative responses in Mammalian lung fibrosis. Science Translational Medicine 2014, 6: 240ra76. PMID: 24920662, PMCID: PMC4340473, DOI: 10.1126/scitranslmed.3007096.
- Cytokine response signatures in disease progression and development of severe clinical outcomes for leptospirosis.Reis EA, Hagan JE, Ribeiro GS, Teixeira-Carvalho A, Martins-Filho OA, Montgomery RR, Shaw AC, Ko AI, Reis MG. Cytokine response signatures in disease progression and development of severe clinical outcomes for leptospirosis. PLoS Neglected Tropical Diseases 2013, 7: e2457. PMID: 24069500, PMCID: PMC3777885, DOI: 10.1371/journal.pntd.0002457.
- Age-dependent dysregulation of innate immunity.Shaw AC, Goldstein DR, Montgomery RR. Age-dependent dysregulation of innate immunity. Nature Reviews. Immunology 2013, 13: 875-87. PMID: 24157572, PMCID: PMC4096436, DOI: 10.1038/nri3547.
- An altered relationship of influenza vaccine-specific IgG responses with T cell immunity occurs with aging in humans.Kang KS, Lee N, Shin MS, Kim SD, Yu Y, Mohanty S, Belshe RB, Montgomery RR, Shaw AC, Kang I. An altered relationship of influenza vaccine-specific IgG responses with T cell immunity occurs with aging in humans. Clinical Immunology (Orlando, Fla.) 2013, 147: 79-88. PMID: 23578549, PMCID: PMC3634098, DOI: 10.1016/j.clim.2013.02.022.
- Age-associated elevation in TLR5 leads to increased inflammatory responses in the elderly.Qian F, Wang X, Zhang L, Chen S, Piecychna M, Allore H, Bockenstedt L, Malawista S, Bucala R, Shaw AC, Fikrig E, Montgomery RR. Age-associated elevation in TLR5 leads to increased inflammatory responses in the elderly. Aging Cell 2012, 11: 104-10. PMID: 22023165, PMCID: PMC3257374, DOI: 10.1111/j.1474-9726.2011.00759.x.
- Age-associated decrease in TLR function in primary human dendritic cells predicts influenza vaccine response.Panda A, Qian F, Mohanty S, van Duin D, Newman FK, Zhang L, Chen S, Towle V, Belshe RB, Fikrig E, Allore HG, Montgomery RR, Shaw AC. Age-associated decrease in TLR function in primary human dendritic cells predicts influenza vaccine response. Journal Of Immunology (Baltimore, Md. : 1950) 2010, 184: 2518-27. PMID: 20100933, PMCID: PMC3867271, DOI: 10.4049/jimmunol.0901022.
- Defective signal transduction in B lymphocytes lacking presenilin proteins.Yagi T, Giallourakis C, Mohanty S, Scheidig C, Shen J, Zheng H, Xavier RJ, Shaw AC. Defective signal transduction in B lymphocytes lacking presenilin proteins. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 979-84. PMID: 18195359, PMCID: PMC2242696, DOI: 10.1073/pnas.0707755105.
- Defective p53 engagement after the induction of DNA damage in cells deficient in topoisomerase 3beta.Mohanty S, Town T, Yagi T, Scheidig C, Kwan KY, Allore HG, Flavell RA, Shaw AC. Defective p53 engagement after the induction of DNA damage in cells deficient in topoisomerase 3beta. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 5063-8. PMID: 18367668, PMCID: PMC2278186, DOI: 10.1073/pnas.0801235105.
- Prevaccine determination of the expression of costimulatory B7 molecules in activated monocytes predicts influenza vaccine responses in young and older adults.van Duin D, Allore HG, Mohanty S, Ginter S, Newman FK, Belshe RB, Medzhitov R, Shaw AC. Prevaccine determination of the expression of costimulatory B7 molecules in activated monocytes predicts influenza vaccine responses in young and older adults. The Journal Of Infectious Diseases 2007, 195: 1590-7. PMID: 17471428, DOI: 10.1086/516788.
- Cytoplasmic tail deletion converts membrane immunoglobulin to a phosphatidylinositol-linked form lacking signaling and efficient antigen internalization functions.Mitchell RN, Shaw AC, Weaver YK, Leder P, Abbas AK. Cytoplasmic tail deletion converts membrane immunoglobulin to a phosphatidylinositol-linked form lacking signaling and efficient antigen internalization functions. The Journal Of Biological Chemistry 1991, 266: 8856-60. PMID: 2026599.
- Mutations of immunoglobulin transmembrane and cytoplasmic domains: effects on intracellular signaling and antigen presentation.Shaw AC, Mitchell RN, Weaver YK, Campos-Torres J, Abbas AK, Leder P. Mutations of immunoglobulin transmembrane and cytoplasmic domains: effects on intracellular signaling and antigen presentation. Cell 1990, 63: 381-92. PMID: 2119890, DOI: 10.1016/0092-8674(90)90171-a.
- Allelic exclusion in transgenic mice that express the membrane form of immunoglobulin mu.Nussenzweig MC, Shaw AC, Sinn E, Danner DB, Holmes KL, Morse HC, Leder P. Allelic exclusion in transgenic mice that express the membrane form of immunoglobulin mu. Science (New York, N.Y.) 1987, 236: 816-9. PMID: 3107126, DOI: 10.1126/science.3107126.
- A human immunoglobulin gene reduces the incidence of lymphomas in c-Myc-bearing transgenic mice.Nussenzweig MC, Schmidt EV, Shaw AC, Sinn E, Campos-Torres J, Mathey-Prevot B, Pattengale PK, Leder P. A human immunoglobulin gene reduces the incidence of lymphomas in c-Myc-bearing transgenic mice. Nature 1988, 336: 446-50. PMID: 3143076, DOI: 10.1038/336446a0.
- Hypovitaminosis D in medical inpatients.Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, Vamvakas EC, Dick IM, Prince RL, Finkelstein JS. Hypovitaminosis D in medical inpatients. The New England Journal Of Medicine 1998, 338: 777-83. PMID: 9504937, DOI: 10.1056/NEJM199803193381201.
- Activated Ras signals developmental progression of recombinase-activating gene (RAG)-deficient pro-B lymphocytes.Shaw AC, Swat W, Ferrini R, Davidson L, Alt FW. Activated Ras signals developmental progression of recombinase-activating gene (RAG)-deficient pro-B lymphocytes. The Journal Of Experimental Medicine 1999, 189: 123-9. PMID: 9874569, PMCID: PMC1887686, DOI: 10.1084/jem.189.1.123.
- Induction of Ig light chain gene rearrangement in heavy chain-deficient B cells by activated Ras.Shaw AC, Swat W, Davidson L, Alt FW. Induction of Ig light chain gene rearrangement in heavy chain-deficient B cells by activated Ras. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 2239-43. PMID: 10051625, PMCID: PMC26767, DOI: 10.1073/pnas.96.5.2239.
- Allelic exclusion in transgenic mice carrying mutant human IgM genes.Nussenzweig MC, Shaw AC, Sinn E, Campos-Torres J, Leder P. Allelic exclusion in transgenic mice carrying mutant human IgM genes. The Journal Of Experimental Medicine 1988, 167: 1969-74. PMID: 3133444, PMCID: PMC2189689, DOI: 10.1084/jem.167.6.1969.
- Delayed production of neutralizing antibodies correlates with fatal COVID-19.Lucas C, Klein J, Sundaram ME, Liu F, Wong P, Silva J, Mao T, Oh JE, Mohanty S, Huang J, Tokuyama M, Lu P, Venkataraman A, Park A, Israelow B, Vogels CBF, Muenker MC, Chang CH, Casanovas-Massana A, Moore AJ, Zell J, Fournier JB, Wyllie AL, Campbell M, Lee A, Chun HJ, Grubaugh ND, Schulz WL, Farhadian S, Dela Cruz C, Ring AM, Shaw AC, Wisnewski AV, Yildirim I, Ko AI, Omer S, Iwasaki A. Delayed production of neutralizing antibodies correlates with fatal COVID-19. Nature Medicine 2021, 27: 1178-1186. PMID: 33953384, PMCID: PMC8785364, DOI: 10.1038/s41591-021-01355-0.
- Author Correction: Delayed production of neutralizing antibodies correlates with fatal COVID-19.Lucas C, Klein J, Sundaram ME, Liu F, Wong P, Silva J, Mao T, Oh JE, Mohanty S, Huang J, Tokuyama M, Lu P, Venkataraman A, Park A, Israelow B, Vogels CBF, Muenker MC, Chang CH, Casanovas-Massana A, Moore AJ, Zell J, Fournier JB, Wyllie AL, Campbell M, Lee AI, Chun HJ, Grubaugh ND, Schulz WL, Farhadian S, Dela Cruz C, Ring AM, Shaw AC, Wisnewski AV, Yildirim I, Ko AI, Omer SB, Iwasaki A. Author Correction: Delayed production of neutralizing antibodies correlates with fatal COVID-19. Nature Medicine 2021, 27: 1309. PMID: 34145437, PMCID: PMC8212078, DOI: 10.1038/s41591-021-01416-4.
- Reply to: A finding of sex similarities rather than differences in COVID-19 outcomes.Takahashi T, Ellingson MK, Wong P, Israelow B, Lucas C, Klein J, Silva J, Mao T, Oh JE, Tokuyama M, Lu P, Venkataraman A, Park A, Liu F, Meir A, Sun J, Wang EY, Casanovas-Massana A, Wyllie AL, Vogels CBF, Earnest R, Lapidus S, Ott IM, Moore AJ, Shaw A, Fournier JB, Odio CD, Farhadian S, Dela Cruz C, Grubaugh ND, Schulz WL, Ring AM, Ko AI, Omer SB, Iwasaki A. Reply to: A finding of sex similarities rather than differences in COVID-19 outcomes. Nature 2021, 597: E10-E11. PMID: 34552250, DOI: 10.1038/s41586-021-03645-6.
- Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity.Lucas C, Vogels CBF, Yildirim I, Rothman JE, Lu P, Monteiro V, Gehlhausen JR, Campbell M, Silva J, Tabachnikova A, Peña-Hernandez MA, Muenker MC, Breban MI, Fauver JR, Mohanty S, Huang J, Shaw AC, Ko AI, Omer SB, Grubaugh ND, Iwasaki A. Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity. Nature 2021, 600: 523-529. PMID: 34634791, DOI: 10.1038/s41586-021-04085-y.
- Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19.Unterman A, Sumida TS, Nouri N, Yan X, Zhao AY, Gasque V, Schupp JC, Asashima H, Liu Y, Cosme C, Deng W, Chen M, Raredon MSB, Hoehn KB, Wang G, Wang Z, DeIuliis G, Ravindra NG, Li N, Castaldi C, Wong P, Fournier J, Bermejo S, Sharma L, Casanovas-Massana A, Vogels CBF, Wyllie AL, Grubaugh ND, Melillo A, Meng H, Stein Y, Minasyan M, Mohanty S, Ruff WE, Cohen I, Raddassi K, Niklason LE, Ko AI, Montgomery RR, Farhadian SF, Iwasaki A, Shaw AC, van Dijk D, Zhao H, Kleinstein SH, Hafler DA, Kaminski N, Dela Cruz CS. Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19. Nature Communications 2022, 13: 440. PMID: 35064122, PMCID: PMC8782894, DOI: 10.1038/s41467-021-27716-4.
- Combining cellular immunology with RNAseq to identify novel chlamydia T cell subset signatures.Johnson RM, Asashima H, Mohanty S, Shaw AC. Combining cellular immunology with RNAseq to identify novel chlamydia T cell subset signatures. The Journal Of Infectious Diseases 2022 PMID: 35172331, DOI: 10.1093/infdis/jiac051.
- Factors associated with retention on medications for opioid use disorder among a cohort of adults seeking treatment in the community.Biondi BE, Vander Wyk B, Schlossberg EF, Shaw A, Springer SA. Factors associated with retention on medications for opioid use disorder among a cohort of adults seeking treatment in the community. Addiction Science & Clinical Practice 2022, 17: 15. PMID: 35255967, PMCID: PMC8899775, DOI: 10.1186/s13722-022-00299-1.
Clinical Trials
Conditions | Study Title |
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Immune System; Men's Health; Women's Health | Effects of circadian regulation and sleep on immune responses |
Diseases of the Nervous System; HIV/AIDS; Infectious Diseases; COVID-19 Inpatient; COVID-19 Outpatient | HIV Associated Reservoirs and Comorbidities (The HARC Plus Study) |
Diseases of the Respiratory Systems; COVID-19 Inpatient; COVID-19 Outpatient | A Study Tracking Health Care Workers Exposed to COVID-19 |
Addictive Behaviors; HIV/AIDS; Infectious Diseases | Impact of HIV Infection on Immunologic, Transcriptomic, and Metabolomic Signatures |