Menno van Zelm performed his PhD studies at the Erasmus MC in Rotterdam, the Netherlands on "B cell development and primary antibody deficiencies" under supervision of Jacques van Dongen and Mirjam van der Burg. These studies resulted in new insights on stepwise human B cell differentiation in bone marrow, and on homeostatic and antigen-induced B cell proliferation with the newly developed KREC assay. Furthermore, Menno described the first antibody-deficient patients with CD19 gene defects. Between 2005 and 2007, he spent 18 months in the laboratory of Kees Murre at the University of California San Diego (UCSD) on the structural organization of the Ig heavy chain locus in developing B cells.

In 2008, A/Prof van Zelm returned to Rotterdam for postdoctoral studies on CD19-complex deficiencies and he identified the first CD81 deficiency. From 2009, he headed a research group in the Erasmus MC (since 2013 as associate professor), and works on the regulation of Ig repertoire formation in precursor-B-cell development and the generation of memory B cells and plasma cells. Most studies involve human material to allow direct translation to patient care. Current disease models include antibody deficiencies, Down syndrome, persistent viral infections, auto-inflammatory diseases and IgE-mediated allergies. He moved to Monash University in 2015.

A/Prof van Zelm has received multiple personal grants since 2009, including a Veni Fellowship from the Netherlands Organisation for Scientific Research (NWO). In 2010, he received the Heineken Young Scientists Award from the Royal Netherlands Academy of Sciences (KNAW).

A/Prof van Zelm is an academic editor for the international journals PLoS One, Frontiers in Immunology, and Immunology and Cell Biology. He is vice chair of the IUIS Nomenclature committee and a council member of the Human Cell Differentiation Molecules (HCDM) organisation that assigns new CD nomenclature and currently evaluates expression patterns of previously assigned CD markers in the CDMaps project.