Dr. Mehdi Arbabi-Ghahroudi

Biography

Dr. Mehdi Arbabi is a senior research scientist at the National Research Council Canada and has held Adjunct professor positions at the Carleton University (2010-present) and the University of Guelph (2011-2017). Dr. Arbabi is a pioneer and a leading scientist in the field of Molecular Immunology-single domain antibodies/Nanobodies. The results of his PhD thesis established the proof-of-principle of a novel class of antibodies with unique antigen-binding properties for the first time in the world that was published in well-respected journals including Nature Structural Biology, EMBO, FEBS letter. The findings were indeed, the cornerstone for more than 2500 scientific articles and related-patents published as of 2019, as well as the foundation of a number of Camel Patents filed between the years 1995-2001, leading to the establishment of the Belgium biotech company Ablynx in 2001(now acquired by Sanofi) and the very first FDA-approved Nanobody-based drug Caplacizumab in 2018.  Dr. Arbabi got his honour B.Sc. degree in Genetics, M. Sc. degree in Molecular Biology, and his PhD in Molecular Biology/Immunology from the Free University of Brussels (Vrij Universiteit Brussel; VUB), Belgium. In 2004, Dr. Arbabi joined Antibody Engineering Group in Human Health Therapeutics research center at National Research Council of Canada- as a Research Scientist where he contributed significantly in the establishment of Camelidae and human single domain antibody platform technology. Dr. Arbabi got an NRC industrial partnership (with Novartis Company) award in 2011 for his excellent contribution in human single domain technology development. In 2016, he got a second NRC outstanding achievement award (Research and Technology Breakthrough) in developing Nanobodies which could cross blood-brain barrier.  Dr Arbabi has so far published more than 50 peer-reviewed scientific articles, book chapters and has been the inventor of 12 different patents at the NRC. A close-to one million dollar Weston Brain Institute grant was recently awarded to the NRC-BMI Team in which Dr. Arbabi plays a major role in identifying functional and blocking nanobodies against NLRP component of inflamasome complex for the treatment of chronic neurodegenerative diseases.

Research Interests

Performing advanced and innovative research in the area of antibody engineering, particularly with single-domain antibodies (sdAbs), and Phage Display and other in vitro display technologies.  Engineered antibodies, and in particular bi-and multi-specific antibodies, could be efficiently applied in combating cancer, neurological, bacterial and viral diseases. They would also be effective as immunohistochemical, diagnostic and proteomic reagents and in environmental applications. .Another exciting line of research in the field of sdAbs is developing novel class of single domain antibodies which are capable of blocking/modulating ion channel function. These novel target-specific reagents could replace chemical drugs in pain management in near future.

Publications

• Lindo, Lorenzo, Waller, Daniel, Selleri, Silvia, Chesi, Marta, Bergsagel, Leif, Arbabi Ghahroudi, Mehdi, McComb, Scott and Hay, Kevin. 2022.  BCMA CAR T-cells secreting IL-12 to alter the tumour microenvironment in multiple myeloma; vol22; 10.1016/S2152-2650(22)00279-8.
• Mehdi Arbabi-Ghahroudi. 2022. Camelid Single-Domain Antibodies: promises and challenges as lifesaving treatments. Int J Mol Sci.; 23(9):5009. doi: 10.3390/ijms23095009.
• Henry KA, Nguyen TD, Baral TN, Hussack G, Raphael S, Arbabi-Ghahroudi M, Robert A, Durocher Y, Wu C, Jaramillo ML, MacKenzie CR. 2021 Biparatopic single-domain antibodies against Axl achieve ultra-high affinity through intramolecular engagement. Biochem Biophys Res Commun.; 562:154-161. doi: 10.1016/j.bbrc.2021.05.030.
• Henry KA, Hussack G, Kumaran J, Gilbert M, MacKenzie CR, Sulea T, Arbabi-Ghahroudi M. 2019. Role of the non-hypervariable FR3 D-E loop in single-domain antibody recognition of haptens and carbohydrates. J Mol Recognit: e2805. doi: 10.1002/jmr.2805.
• Rossotti MA, Henry KA, van Faassen H, Tanha J, Callaghan D, Hussack G, MacKenzie CR and  Arbabi-Ghahroudi M. 2019. Camelid single-domain antibodies raised by DNA immunization are potent inhibitors of EGFR signaling. Biochem J. 476(1):39-50. doi: 10.1042/BCJ20180795.
• Bertrand MJ, Abran M, Maafi F, Busseuil D, Merlet N, Mihalache-Avram T, Geoffroy P, Tardif PL, Abulrob A, Arbabi-Ghahroudi M, Ni F, Sirois M, L'Allier PL, Rhéaume É, Lesage F, Tardif JC. 2019. In Vivo Near-Infrared Fluorescence Imaging of Atherosclerosis Using Local Delivery of Novel Targeted Molecular Probes. Nature Scientific Reports 9(1): 2670(1-11). doi: 10.1038/s41598-019-38970-4
• **Arbabi-Ghahroudi M. 2017. Camelid Single-Domain Antibodies: Historical Perspective and Future Outlook. Front Immunol.  8: 1-8. doi: 10.3389/fimmu.2017.01589. 

• Camelid single domain antibodies revolutionized the field of antibody engineering and their applications and I am proud to be part of the original discovery team back in the 1990s in Brussels, Belgium. Our original work on this topic has been cited 661 times as of March 18, 2018.

• Henry KA, Sulea T, van Faassen H, Hussack G, Purisima EO, MacKenzie CR, Arbabi-Ghahroudi M. 2016. A Rational Engineering Strategy for Designing Protein A-Binding Camelid Single-Domain Antibodies. PLoS One 11(9): 1-18. doi: 10.1371/journal.pone.0163113.
• Henry KA, Arbabi-Ghahroudi M, Scott JK. 2015. Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold. Front Microbiol 6:755, 1-18. 10.3389/fmicb.2015.00755.
• Kandalaft H, Hussack G, Aubry A, van Faassen H, Guan Y, Arbabi-Ghahroudi M, MacKenzie R, Logan SM, Tanha J. 2015. Targeting surface-layer proteins with single-domain antibodies: a potential therapeutic approach against Clostridium difficile-associated disease. Appl Microbiol Biotechnol 99:8549-8562.
• Gene RW, Kumaran J, Aroche C, van Faassen H, Hall JC, MacKenzie CR, Arbabi-Ghahroudi M. 2015. High affinity anti-Internalin B VHH antibody fragments isolated from naturally and artificially immunized repertoires. J Immunol Methods 416:29-39.
• Hussack G, Riazi A, Ryan S, van Faassen H, MacKenzie R, Tanha J, Arbabi-Ghahroudi M.2014. Protease resistant Campylobacter jejuni-specific V_HHs that potently inhibit bacterial motility. Prot Eng Des Sel 27:191-8.
• **Riazi A, Strong PCR, Coleman R, Chen W, Hirama T, van Faassen H, Henry M, Logan SM, Szymanski CS, MacKenzie R, Arbabi-Ghahroudi, M. 2013. Pentavalent single-domain antibodies reduce Campylobacter jejunimotility and colonization in chickens.PLOS ONE 8(12):e83928.

• DOW AgroScienes abandoned the Campylobacter project in 2010 and I capitalized on interest from AbCelex Technologies Inc. in further exploring the potential application of anti-Campylobacter antibodies for oral delivery in chickens.

• Richard G, Meyers AJ, McLean MD, Arbabi-Ghahroudi M, MacKenzie R, Hall JC. 2013. In vivo neutralization of a-cobratoxin with high affinity llama single domain antibodies (V_HHs) and a V_HH-Fc antibody. PLOS ONE 8(7) e69495.
• Ayat H, Burrone OR, Sadghizadeh M, Jahanzad E, Rastgou N, Moghadasi S, Arbabi M. 2013.Isolation of scFv antibody fragments against HER2 and CEA tumor antigens from combinatorial antibody libraries derived from cancer patients. Biologicals41:345-354.
• Hussack G, Keklikian A, Alsughayyir J, Hanifi-Moghaddam P, Arbabi-Ghahroudi M, van Faassen H, Hou ST, Sad S, MacKenzie R, Tanha J. 2012. A VL single-domain antibody library shows a high-propensity to yield non-aggregating binders. Prot Eng Des Sel25:313-188.
• Baral TN, Chao SY, Li S, Tanha J, Arbabi-Ghahroudi M, Zhang J, Wang S. 2012. Crystal structure of a human single domain antibody dimer formed through VH-VH non-covalent interactions. PLOS One, 7(1):e30149.
• Makvandi-Nejad S, Fjällman T, Arbabi-Ghahroudi M, MacKenzie CR, Hall JC. 2011. Selection and expression of recombinant single domain antibodies from a hyper-immunized library against the hapten azoxystrobin. J Immunol Methods 373:8-18.
• Hussack, G, Arbabi-Ghahroudi, M, Hirama, T, Songer, JG, MacKenzie CR, Tanha J.2011.Neutralization of Clostridium difficile toxin A with single-domain antibodies targeting the cell-receptor binding domain. J Biol Chem286:8961-76.
• Salavatifar M, Amin S, Jahromi ZM, Rasgoo N, Rastgoo N and Arbabi-Ghahroudi M. 2011. Green fluorescent-conjugated anti-CEA single chain antibody for the detection of CEA-positive cancer cells. Hybridoma 30:229-38.
• Iqbal U, Albaghdadi H, Luo Y, Arbabi M, Desvaux C, Veres T, Stanimirovic D, Abulrob A. 2010. Molecular imaging of glioblastoma multiforme using anti-insulin-like growth factor-binding protein-7 single-domain antibodies. Br J Cancer 103:1606-16.
• Doyle, PJ, Saeed H, Hermans, A, Gleddie SC, Hussack G, Arbabi-Ghahroudi M, Seguin C, Savard, ME, MacKenzie CR, Hall JC. 2009. Intracellular expression of a single domain antibody reduces cytotoxicity of 15-acetyldeoxynivalenol in yeast. J Biol Chem 284:35029-39.
• Bell A, Wang ZJ, Arbabi Ghahroudi M, Chang TA, Durocher Y, Trojahn U, Baardsnes J, Jaramillo M, Li S, Baral TN, O’Connor-McCourt M, MacKenzie R, Zhang J. 2010. Differential tumor-targeting abilities of three single-domain antibody formats. Cancer Lett 289:81-90.
• **Arbabi-Ghahroudi M, To R, Gaudette N, Hirama T, Ding W, MacKenzie R, Tanha J. 2008. Aggregation-resistant V_Hs selected by in vitro evolution tend to have disulfide-bonded loops and acidic isoelectric points. Prot Eng Des Sel22:59-66.

• This work established the potential application of human VH semi-synthetic libraries in isolating fully human single domain antibodies specific to therapeutically important targets and was part of the IP package which brought 1.2 M revenue to the NRC.

• Arbabi-Ghahroudi M, Tanha J, MacKenzie R. 2005. Prokaryotic expression of antibodies. Cancer Metastasis Rev 24:501-519.