Brown's research primarily focuses on the areas of molecular biology and microbiology. At the beginning of his career, he explored several aspects of molecular biology, with a particular focus on the genetic code. Later his work was aimed at understanding the fundamentals of microbiology and virology and several aspects related to it. Thereafter, he and his team began to work on the structural and functional properties of herpes simplex virus. More recently, he has branched out into human gene expression.[7]
Brown's current research revolves around the control of human gene expression and Organization of transcription factor binding sites in the promoters of human genes. He has co-written more than 100 peer-reviewed articles for leading journals and has been cited broadly throughout his career.[8]
Brown began his work in molecular biology with a substantial interest in the genetic code. During his PhD, under the supervision of Paul Doty, he proposed the development of new methods to synthesize oligonucleotides of defined sequence and studied their coding properties.[9] Subsequently, he demonstrated that the incorporation of N-formylmethionine is stimulated by oligonucleotide messengers that contain the sequence AUG near or at the 5' end of the messenger RNA chain and that it does not stimulate unformulated methionine.[10] He further revealed that AUG is capable of encoding methionine for both initiating and extension methionines.[11]
Following that Brown has worked on the surface glycoproteins and revealed a cell surface glycoprotein characterized as a differentiated state of neuroblastoma C-1300 cells.[12] In his research, he has elucidated significant differences in the amounts of 4 glycopeptide classes extracted from vertebrate cells and also detected a glycopeptide which was only present during the cell-division period and named it glycol-peptide 4.[13] He also identified differential properties of cell surface membrane from the internal membrane, and particularly highlighted that the isolation of glycoproteins with smooth membrane fraction of cell homogenates characterizes them from internal glycoproteins. Based on these criteria, he isolated two molecular weight classes of glycoproteins as the constituents of the plasma membrane of mouse L-929 cells[14] and suggested that band 1 polypeptide might be efficiently involved in regulating L cell growth.[15]
Whilst working on gene expression, he proposed that for the protection of promoter's ability to regulate gene expression from the mutagenic damage the transcription binding sites of promoters are arrayed in multiple forms and ascertained supportive evidence in brain and liver-specific gene expression.[16]
Brown has worked widely on vesicular stomatitis virus, herpes simplex virus, and human papilloma virus. His research justified the view that the vesicular stomatitis virus matrix M (VSV-M) protein plays a vital role in the maintenance of nucleocapsid in a compact form[17] and mentioned the possibility of identical functionality of VSV-M in-vivo.[18] While working on the physical characteristics of N protein of vesicular stomatitis virus through electron microscopy images he inferred that the N protein has a bilobed structure and is wedge-shaped with an approximate 9.0 nm, 5.0 nm, and 3.3 nm of length, depth, and width respectively.[19] In 1991, he started working on Human papilloma virus and published its structure using cryoelectron microscopy. His work clarified that the structural capsid hexon of the human papilloma virus is molecular pentameres.[20]
A major part of Brown's work was on herpes simplex virus (HSV) and mainly focuses on its structure[2] and assembly to determine properties that can aid in the development of novel anti-herpes therapeutic drugs. He illustrated the molecular composition of the capsid pentons and the triplexes of HSV 1 using the guanidine-HCl extraction[21] and discovered that the protein of abortive capsids of equine herpes virus is entirely encapsulated within the capsid.[22] Later, he detected that the HSV capsid assembles in a cell-free environment with the help of four capsid proteins, including VP5 as the major capsid protein, VP22a as a scaffolding protein and VP19c and VP23 as triplex proteins.[23] In related research, he discovered that a mature, icosahedral herpes simplex virus capsid is formed by a spherical intermediate named procapsid,[24] studied the maturation of procapsid through cryoelectron microscopy[25] and described the distinct structural and conformational changes that occur when a procapsid and is transformed into a mature one.[26] Furthermore, he identified the portal that allows entry and exit of herpes virus DNA from the capsid, at the capsid vertex and also demonstrated the isolation of intact capsid from insect cells that produce pUL6 protein.[27]
