Pelham is an authority on the movement of proteins within cells. Pelhams's work has explained how some proteins can protect cells from damage. He has also shown how cells remove damaged or unwanted proteins – vital for maintaining their healthy functioning. More recently, his research investigates how proteins are modified and sorted to their correct places within cells and aims to find ways of blocking these processes.[7][10][11][12][13]
Distinguished for his contributions to protein biosynthesis, the control of gene activity and intracellular sorting. He developed a sensitive in vitro translation system, with which he discovered that naturally "leaky" termination codons exist in plant virus RNAs, and achieved the first correct synthesis and processing of viral polyproteins in vitro. He showed that the transcription factorTFIIIA, which is required in Xenopusoocytes for 5S rDNA transcription, binds to the gene product, %S RNA and is present in large amounts in oocytes. From studies on heat shock genes, he identified the first regulatory DNA sequence (the "Pelham" box) in a eukaryotic gene, proving this alone could confer heat inducibility on another gene. He has shown that this sequence is the binding site for a transcription factor which is modified by heat shock, thus establishing the basic mechanism of induction of these genes. He has clarified the function of heat shock proteins, finding that two of these reside in the lumen of the endoplasmic reticulum. This led to his discovery that a C-terminalamino acid sequence is a novel sorting signal, preventing proteins from being exported from the lumen of the endoplasmic reticulum.[14]