Research Profile

Andrew Lindsay

Biography

Dr Andrew Lindsay is a graduate of Trinity College Dublin and obtained a PhD from University College Cork. He has previously worked in the Department of Medical and Molecular Genetics in the Indiana University School of Medicine and at the Institut Curie, Paris. He is currently an independent investigator in the School of Biochemistry and Cell Biology, UCC.

His group studies the endosomal recycling pathway, and the role that its dysregulation plays in the aggressiveness of certain cancers. This pathway is the main cellular mechanism for controlling the composition of the plasma membrane.  Research from his lab has shown that inhibiting endosomal recycling reduces the metastatic potential of cancer cells, and can also enhance the effectiveness of a number of targeted therapies.

Dr Lindsay has received a number of grants including a HRB Career Development Award and a Marie Curie Research Fellowship. The main focus of his laboratory is to identify and characterise small-molecule inhibitors of the endosomal recycling pathway that may be useful as novel anti-cancer therapies.

Research Interests

My research is focused primarily on the study of intracellular membrane trafficking, in particular the endosomal recycling pathway. This pathway is the main cellular mechanism for controlling the composition of the plasma membrane. Receptor tyrosine kinases (RTKs), integrins, G-protein coupled receptors, matrix metalloproteinases (MMPs), and cadherins are examples of cell surface proteins that undergo endocytic recycling. Defects in this pathway have been linked to a number of diseases including neurological disorders such as Huntington’s disease and Griscelli’s Syndrome Type I, and intestinal disorders such as microvillus inclusion disease. Furthermore, a number of intracellular pathogens such as HIV and Chlamydia trachomatis ‘hijack’ the endosomal recycling pathway during their life cycle.

In recent years it has emerged that aberrant expression of key regulators of endosomal recycling can lead to the increased aggressiveness of a wide range of cancers. One such regulator is a protein that I identified during my PhD called Rab Coupling Protein (RCP). The RCP gene is frequently amplified in breast cancer and has been found to be a breast cancer promoting gene. Downregulation of RCP inhibits the motility and invasiveness (key properties of metastatic tumour cells) of lung and breast cancer cells.

The main goals of my research are to gain a greater understanding of the role that a malfunctioning endosomal recycling pathway plays in cancer metastasis, with a view to identifying novel therapeutic targets. Greater than 90% of all deaths caused by solid cancers result from metastasis, i.e. the formation of secondary tumours in distant organs such as the lungs, liver, brain and bone. Given the importance of the endosomal recycling pathway in mediating the aggressiveness of cancers (likely due to biased recycling of adhesion molecules, MMPs, integrins, and RTKs), a major focus is to identify inhibitors of endosomal recycling that will have therapeutic potential as anti-metastatic cancer drugs.

 We use a wide range of techniques including molecular biology, bioinformatics, protein biochemistry, cell culture, genetics, and fluorescent imaging. In particular I would consider myself to be a specialist in advanced cell imaging. I regularly use cutting edge techniques such as FRET, FRAP, super resolution microscopy, TIRF, quantitative colocalisation analysis etc.

 

Research Grants

 ProjectFunding
Body
Start DateEnd DateAward
Characterisation of the Role of the Human Myosin V Family in Cell Division and Disease.Health Research Board01-OCT-0530-SEP-08€225,000.00
Characterisation of the Role and Regulation of Myosin Va in Membrane Transport and DiseaseHealth Research Board01-JAN-1001-FEB-13€280,186.00

Publications

Book Chapters

 YearPublication
(2015)'Rabs of the Endosomal Recycling Pathway'
Lindsay A.J., McCaffrey M.W. (2015) 'Rabs of the Endosomal Recycling Pathway' In: Encyclopedia of Cell Biology. London: Elsevier. [Details]
(2005)'Functional properties of the Rab-binding domain of Rab coupling protein'
Lindsay, AJ;Marie, N;McCaffrey, MW (2005) 'Functional properties of the Rab-binding domain of Rab coupling protein' In: GTPASES REGULATING MEMBRANE TARGETING AND FUSION. SAN DIEGO: ELSEVIER ACADEMIC PRESS INC. [DOI] [Details]
(2005)'Purification and functional properties of Rab11-FIP2'
Lindsay, AJ;McCaffrey, MW (2005) 'Purification and functional properties of Rab11-FIP2' In: GTPASES REGULATING MEMBRANE TARGETING AND FUSION. SAN DIEGO: ELSEVIER ACADEMIC PRESS INC. [DOI] [Details]
(2013)'Rab Family'
McCaffrey M.W., Lindsay A.J. (2013) 'Rab Family' In: Encyclopedia of Biological Chemistry. London: Elsevier. [Details]
(2005)'Pruification and Functional properties of Rab11-FIP2'
Lindsay, A.J., McCaffrey, M.W.; (2005) 'Pruification and Functional properties of Rab11-FIP2' In: Methods in Enzymology. USA: Academic Press. [Details]
(2005)'Functional Properties of the Rab-Binding Domain of Rab Coupling Protein'
Lindsay AJ, Marie N, McCaffrey MW (2005) 'Functional Properties of the Rab-Binding Domain of Rab Coupling Protein' In: W. Balch, C. Der, A. Hall (eds). Methods in Enzymology. NA: Academic Press. [Details]
(2005)'Functional properties of the Rab-Binding Domain of Rab Coupling Protein'
Lindsay, A.J., Marie, N., M.W. McCaffrey; (2005) 'Functional properties of the Rab-Binding Domain of Rab Coupling Protein' In: Methods in Enxymology, 403, GTPases Regulating Membrane Targeting and Fusion. [Details]
(2004)'The Rab Family'
McCaffrey, M.W., Lindsay, A.J.; (2004) 'The Rab Family' In: Encyclopedia of Biological Chemistry. [Details]

Peer Reviewed Journals

 YearPublication
(2019)'Rab32 interacts with SNX6 and affects retromer-dependent Golgi trafficking'
Waschbusch, D;Hubel, N;Ossendorf, E;Lobbestael, E;Baekelandt, V;Lindsay, AJ;McCaffrey, MW;Khan, AR;Barnekow, A (2019) 'Rab32 interacts with SNX6 and affects retromer-dependent Golgi trafficking'. Plos One, 14 [DOI] [Details]
(2017)'Rab11 family expression in the human placenta: Localization at the maternal-fetal interface'
Taglauer, ES;Artemiuk, PA;Hanscom, SR;Lindsay, AJ;Wuebbolt, D;Breathnach, FM;Tully, EC;Khan, AR;McCaffrey, MW (2017) 'Rab11 family expression in the human placenta: Localization at the maternal-fetal interface'. Plos One, 12 [DOI] [Details]
(2017)'Regulation of NF-kappa B by PML and PML-RAR alpha'
Ahmed, A;Wan, XC;Mitxitorena, I;Lindsay, AJ;Pandolfi, PP;McCaffrey, MW;Keeshan, K;Chen, YHH;Carmody, RJ (2017) 'Regulation of NF-kappa B by PML and PML-RAR alpha'. Scientific Reports, 7 [DOI] [Details]
(2016)'Rab coupling protein mediated endosomal recycling of N-cadherin influences cell motility'
Lindsay AJ;McCaffrey MW; (2016) 'Rab coupling protein mediated endosomal recycling of N-cadherin influences cell motility'. Oncotarget, [DOI] [Details]
(2015)'Structure-Function Analyses of the Interactions between Rab11 and Rab14 Small GTPases with Their Shared Effector Rab Coupling Protein (RCP)'
Lall, P;Lindsay, AJ;Hanscom, S;Kecman, T;Taglauer, ES;McVeigh, UM;Franklin, E;McCaffrey, MW;Khan, AR (2015) 'Structure-Function Analyses of the Interactions between Rab11 and Rab14 Small GTPases with Their Shared Effector Rab Coupling Protein (RCP)'. Journal of Biological Chemistry, 290 :18817-18832 [DOI] [Details]
(2012)'Roles for myosin Va in RNA transport and turnover'
McCaffrey, MW;Lindsay, AJ (2012) 'Roles for myosin Va in RNA transport and turnover'. Biochemical Society Transactions, 40 :1416-1420 [DOI] [Details]
(2012)'Roles for myosin Va in RNA transport and turnover'
McCaffrey M.W., Lindsay A.J. (2012) 'Roles for myosin Va in RNA transport and turnover'. Biochemical Society Transactions, 40 (6):1416-1420 [Details]
(2011)'Myosin Va Is Required for P Body but Not Stress Granule Formation'
Lindsay, AJ;McCaffrey, MW (2011) 'Myosin Va Is Required for P Body but Not Stress Granule Formation'. Journal of Biological Chemistry, 286 :11519-11528 [DOI] [Details]
(2007)'Rip11 is a Rab11- and AS160-RabGAP-binding protein required for insulin-stimulated glucose uptake in adipocytes'
Welsh GI, Leney SE, Lloyd-Lewis B, Wherlock M, Lindsay AJ, McCaffrey MW, Tavaré JM; (2007) 'Rip11 is a Rab11- and AS160-RabGAP-binding protein required for insulin-stimulated glucose uptake in adipocytes'. Journal of cell science, 120 (Pt 23):4197-4208 [DOI] [Details]
(2007)'Rip11 is a Rab11-and AS160-RabGAP-binding protein required for insulin-stimulated glucose uptake in adipocytes'
Welsh, GI;Leney, SE;Lloyd-Lewis, B;Wherlock, M;Lindsay, AJ;McCaffrey, MW;Tavare, JM (2007) 'Rip11 is a Rab11-and AS160-RabGAP-binding protein required for insulin-stimulated glucose uptake in adipocytes'. Journal of Cell Science, 120 :4197-4208 [DOI] [Details]
(2006)'Crystal structure of Rab11 in complex with Rab11 family interacting protein 2'
Jagoe, WN;Lindsay, AJ;Read, RJ;Mccoy, AJ;McCaffrey, MW;Khan, AR (2006) 'Crystal structure of Rab11 in complex with Rab11 family interacting protein 2'. Structure, 14 :1273-1283 [DOI] [Details]
(2004)'Rab coupling protein associates with phagosomes and regulates recycling from the phagosomal compartment'
Damiani, MT;Pavarotti, M;Leiva, N;Lindsay, AJ;McCaffrey, MW;Colombo, MI (2004) 'Rab coupling protein associates with phagosomes and regulates recycling from the phagosomal compartment'. Traffic, 5 :785-797 [DOI] [Details]
(2004)'Characterisation of the Rab binding properties of Rab coupling protein (RCP) by site-directed mutagenesis'
Lindsay, AJ;McCaffrey, MW (2004) 'Characterisation of the Rab binding properties of Rab coupling protein (RCP) by site-directed mutagenesis'. Febs Letters, 571 :86-92 [DOI] [Details]
(2002)'Rab11-FIP4 interacts with Rab11 in a GTP-dependent manner and its overexpression condenses the Rab11 positive compartment in HeLa cells'
Wallace, DME;Lindsay, AJ;Hendrick, AG;McCaffrey, MW (2002) 'Rab11-FIP4 interacts with Rab11 in a GTP-dependent manner and its overexpression condenses the Rab11 positive compartment in HeLa cells'. Biochemical and Biophysical Research Communications, 299 :770-779 [Details]
(2002)'The novel Rab11-FIP/Rip/RCP family of proteins displays extensive homo- and hetero-interacting abilities'
Wallace, DM;Lindsay, AJ;Hendrick, AG;McCaffrey, MW (2002) 'The novel Rab11-FIP/Rip/RCP family of proteins displays extensive homo- and hetero-interacting abilities'. Biochemical and Biophysical Research Communications, 292 :909-915 [DOI] [Details]
(2016)'Congenital macrothrombocytopenia-linked mutations in the actin-binding domain of alpha-actinin-1 enhance F-actin association'
Murphy, ACH;Lindsay, AJ;McCaffrey, MW;Djinovic-Carugo, K;Young, PW (2016) 'Congenital macrothrombocytopenia-linked mutations in the actin-binding domain of alpha-actinin-1 enhance F-actin association'. Febs Letters, 590 :685-695 [DOI] [Details]
(2015)'Structure-Function Analyses of the Interactions between Rab11 and Rab14 Small GTPases with Their Shared Effector Rab Coupling Protein (RCP)'
Lall P, Lindsay AJ;Hanscom S;Kecman T;Taglauer ES;McVeigh UM;Franklin E;McCaffrey MW;Khan AR (2015) 'Structure-Function Analyses of the Interactions between Rab11 and Rab14 Small GTPases with Their Shared Effector Rab Coupling Protein (RCP)'. The Journal of Biological Chemistry, 290 (30):18817-18832 [DOI] [Details]
(2015)'Analysis of the interactions between Rab GTPases and class V myosins'
Lindsay AJ, Miserey-Lenkei S;Goud B (2015) 'Analysis of the interactions between Rab GTPases and class V myosins'. Methods of Molecular Biology, 1298 :73-83 [DOI] [Details]
(2015)'Rab antibody characterization: comparison of Rab14 antibodies'
Lindsay AJ, McCaffrey MW (2015) 'Rab antibody characterization: comparison of Rab14 antibodies'. Methods of Molecular Biology, 1298 :161-171 [DOI] [Details]
(2014)'Myosin Va is required for the transport of fragile X mental retardation protein (FMRP) granules'
Lindsay AJ, McCaffrey MW (2014) 'Myosin Va is required for the transport of fragile X mental retardation protein (FMRP) granules'. Biology of The Cell / Under The Auspices of The European Cell Biology Organization, 106 (2):57-71 [DOI] [Details]
(2013)'Identification and characterization of multiple novel Rab-myosin Va interactions'
Lindsay AJ, Jollivet F, Horgan CP, Khan AR, Raposo G, McCaffrey MW, Goud B (2013) 'Identification and characterization of multiple novel Rab-myosin Va interactions'. Molecular Biology of The Cell, 24 (21):3420-3434 [DOI] [Details]
(2012)'Roles for myosin Va in RNA transport and turnover'
McCaffrey MW, Lindsay AJ (2012) 'Roles for myosin Va in RNA transport and turnover'. Biochemical Society transactions, 40 (6):1416-1420 [DOI] [Details]
(2010)'Myristoylation of the dual-specificity phosphatase c-JUN N-terminal kinase (JNK) stimulatory phosphatase 1 is necessary for its activation of JNK signaling and apoptosis'
Schwertassek U, Buckley DA, Xu CF, Lindsay AJ, McCaffrey MW, Neubert TA, Tonks NK; (2010) 'Myristoylation of the dual-specificity phosphatase c-JUN N-terminal kinase (JNK) stimulatory phosphatase 1 is necessary for its activation of JNK signaling and apoptosis'. Febs Journal, 277 (11):2463-2473 [DOI] [Details]
(2009)'Myosin Vb localises to nucleoli and associates with the RNA polymerase I transcription complex'
Lindsay AJ, McCaffrey MW; (2009) 'Myosin Vb localises to nucleoli and associates with the RNA polymerase I transcription complex'. Cell Motility and The Cytoskeleton, [DOI] [Details]
(2008)'Rab-coupling protein coordinates recycling of alpha5beta1 integrin and EGFR1 to promote cell migration in 3D microenvironments'
Caswell PT, Chan M, Lindsay AJ, McCaffrey MW, Boettiger D, Norman JC; (2008) 'Rab-coupling protein coordinates recycling of alpha5beta1 integrin and EGFR1 to promote cell migration in 3D microenvironments'. The Journal of Cell Biology, 183 (1):143-155 [DOI] [Details]
(2006)'Purification, crystallization and preliminary X-ray diffraction studies of Rab11 in complex with Rab11-FIP2'
Jagoe WN, Jackson SR, Lindsay AJ, McCaffrey MW, Khan AR; (2006) 'Purification, crystallization and preliminary X-ray diffraction studies of Rab11 in complex with Rab11-FIP2'. Acta Crystallographica. Section F, Structural Biology and Crystallization Communications, 62 (Pt 7):692-694 [DOI] [Details]
(2005)'Rab coupling protein is selectively degraded by calpain in a Ca2+-dependent manner'
Marie N, Lindsay AJ, McCaffrey MW; (2005) 'Rab coupling protein is selectively degraded by calpain in a Ca2+-dependent manner'. The Biochemical Journal, 389 (Pt 1):223-231 [DOI] [Details]
(2005)'Functional properties of the Rab-binding domain of Rab coupling protein'
Lindsay AJ, Marie N, McCaffrey MW; (2005) 'Functional properties of the Rab-binding domain of Rab coupling protein'. Methods in enzymology, 403 :481-491 [DOI] [Details]
(2005)'Rab coupling protein is selectively degraded by calpain in a Ca2+-dependent manner'
Marie, N,Lindsay, AJ,McCaffrey, MW; (2005) 'Rab coupling protein is selectively degraded by calpain in a Ca2+-dependent manner'. The Biochemical Journal, 389 :223-231 [DOI] [Details]
(2005)'Purification and functional properties of Rab11-FIP2'
Lindsay AJ, McCaffrey MW; (2005) 'Purification and functional properties of Rab11-FIP2'. Methods In Enzymology, 403 :491-499 [DOI] [Details]
(2004)'The C2 domains of the class I Rab11 family of interacting proteins target recycling vesicles to the plasma membrane'
Lindsay AJ, McCaffrey MW; (2004) 'The C2 domains of the class I Rab11 family of interacting proteins target recycling vesicles to the plasma membrane'. Journal of Cell Science, 117 (Pt 19):4365-4375 [DOI] [Details]
(2004)'Rab coupling protein associates with phagosomes and regulates recycling from the phagosomal compartment'
Damiani MT, Pavarotti M, Leiva N, Lindsay AJ, McCaffrey MW, Colombo MI; (2004) 'Rab coupling protein associates with phagosomes and regulates recycling from the phagosomal compartment'. Traffic (Copenhagen, Denmark), 5 (10):785-797 [DOI] [Details]
(2002)'Rab11-FIP2 functions in transferrin recycling and associates with endosomal membranes via its COOH-terminal domain'
Lindsay, AJ,McCaffrey, MW; (2002) 'Rab11-FIP2 functions in transferrin recycling and associates with endosomal membranes via its COOH-terminal domain'. The Journal of Biological Chemistry, 277 :27193-27199 [DOI] [Details]
(2002)'Rab coupling protein (RCP), a novel Rab4 and Rab11 effector protein'
Lindsay, AJ,Hendrick, AG,Cantalupo, G,Senic-Matuglia, F,Goud, B,Bucci, C,McCaffrey, MW; (2002) 'Rab coupling protein (RCP), a novel Rab4 and Rab11 effector protein'. The Journal of Biological Chemistry, 277 :12190-12199 [DOI] [Details]
(2002)'The novel Rab11-FIP/Rip/RCP family of proteins displays extensive homo- and hetero-interacting abilities'
Wallace DM, Lindsay AJ, Hendrick AG, McCaffrey MW; (2002) 'The novel Rab11-FIP/Rip/RCP family of proteins displays extensive homo- and hetero-interacting abilities'. Biochemical and Biophysical Research Communications, 292 (4):909-915 [DOI] [Details]
(2002)'Rab11-FIP4 interacts with Rab11 in a GTP-dependent manner and its overexpression condenses the Rab11 positive compartment in HeLa cells'
Wallace, DME,Lindsay, AJ,Hendrick, AG,McCaffrey, MW; (2002) 'Rab11-FIP4 interacts with Rab11 in a GTP-dependent manner and its overexpression condenses the Rab11 positive compartment in HeLa cells'. Biochemical and Biophysical Research Communications, 299 :770-779 [DOI] [Details]
(1997)'Acute phase proteins in salmonids: evolutionary analyses and acute phase response'
Jensen LE, Hiney MP, Shields DC, Uhlar CM, Lindsay AJ, Whitehead AS (1997) 'Acute phase proteins in salmonids: evolutionary analyses and acute phase response'. Journal of immunology (Baltimore, Md. : 1950), 158 (1):384-392 [Details]

Professional Activities

Professional Associations

 AssociationFunctionFrom / To
American Society of Cell Biology Professional Society/
Irish Association for Cancer Research IACR/
Biochemical Society Professional Society/
Institute of Leadership and Management Professional Society/
Marie Curie Alumni Association Professional Society/

Conference Contributions

 YearPublication
(2006)The American Society for Cell Biology (ASCB) Annual Meeting,
Horgan CP, Lindsay AJ*, Zhdanov AV, Oleksy A, Lall PY, McCaffrey JG and McCaffrey MW (2006) Rab11-FIP3 is required to maintain the endosomal-recycling compartment. [Poster Presentation], The American Society for Cell Biology (ASCB) Annual Meeting, San Diego, California, USA , 09-DEC-06 - 13-DEC-06. [Details]

Journal Activities

 JournalRoleTo / From
Cell Proliferation Referee-
Nature Communications Referee-
Journal Of Cell Science Referee-
Small Referee-

Languages

 LanguageReadingWritingSpeaking
French FunctionalFunctionalFunctional

Outreach Activities

 Description

RTE Brainstorm. Feb 2019

RTE Brainstorm article. June 2018

Primary school outreach programme.

Education

 YearInstitutionQualificationSubject
2016UCC Postgrad Cert. in Teaching & Learning in HETeaching and Learning
2017University College Cork Postgraduate Diploma in Teaching and Learning in Higher EducationTeaching and Learning in Higher Education
1996Trinity College Dublin B.A. (Mod.)Genetics
2002University College Cork PHDBiochemistry and Cell Biology

Other Activities

 Description

Professional Skills for Research Leaders  - 6 month blended learning programme designed to help individual researchers enhance their approach to leadership, management and engagement run by the Insitute of Leadership and Management (ILM). Received ILM Certificate, December 2015.

Occupational First Aid (FETAC Level 5) - Elite Ambulance and Health and Safety, UCC. November 2014


Communication and Media Skills Residential Course – Royal Society, UK. January 2013.

Teaching Activities

Teaching Interests

I have accumulated considerable teaching experience. I endeavour to employ a ‘student-centred’ teaching approach whenever possible. I interact with a broad range of undergraduate and postgraduate students. I deliver Biochemistry and Genetics lectures to first year direct entry medicine students, and to all years of the Biological and Chemical Sciences (CK402) and Genetics (CK405) undergraduate courses in various modules, such as;

·         FM1010 – Introductory Human Biology

·         BC3004 – Cell Signalling

·         GN1006 – Principles and Methods in Genetics

·         GN2001 – Current Perspectives in Genetics

·         GN4002 – Genetics Research Project

·         GN4003 – Genomics and Applications

I also contribute to the following postgraduate modules for the MSc in Molecular Cell Biology with Bioinnovation, Cancer Biology PhD Programme, and MSc in Biomedical Sciences;

·         ML6004 – Cell and Molecular Biology

·         ML6005 – Molecular Techniques in the Life Sciences

I have supervised numerous undergraduate and postgraduate students (PhD and MSc) in Ireland and France, and I am currently supervising an MSc student.

Teaching is something that I am passionate and I am always striving to improve my effectiveness as a teacher. To that end I completed a Postgraduate Certificate in Teaching and Learning in Higher Education (NFQ Level 9) in June 2016, and I am currently undertaking the PG Diploma in Teaching and Learning in Higher Education. These courses provide the tools for third-level teachers to incorporate best practice and the latest technologies into their teaching methods.

Recent Postgraduates

 Graduation YearStudent NameInstitutionDegree TypeThesis Title
2016Rachel O'Carroll University College CorkMSc BioinformaticsA Bioinformatic Approach to Investigating The Role of Membrane Trafficking Proteins in Cancer

Research Information

Internal Collaborators

 NameInstituteCountry
Paul Young University College CorkIRELAND

External Collaborators

 NameOrganisation / InstituteCountry
Amir Khan Trinity College DublinIRELAND
Jim Norman Beatson InstituteSCOTLAND
Jeremy Tavare Bristol UniversityUNITED KINGDOM
Bruno Goud Institut CurieFRANCE

Contact details

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School of Biochemistry and Cell Biology

Scoil na Bithcheimice agus na Cillbhitheolaíochta

University College Cork, Western Road, Cork.

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