Emma is a graduate student in Prof. Pam Silver’s lab and the Laboratory of Systems Pharmacology at Harvard Medical School. For most of her PhD, she has worked on engineering mammalian cells to produce novel steroids. Her current project uses proteomics to study the human innate immune response to DNA in the cytoplasm. Emma’s techniques are as eclectic as her interests; she has used CRISPR-Cas9, small molecule mass spectrometry, HPLC purification, NMR structure identification, protein structure modeling, and pharmacokinetics models in her research.

 

Emma graduated from Swarthmore College with a B.A. in Biochemistry in 2013. She earned High Honors in final exams for seminars in microbial metabolism, protein structure, and environmental chemistry. Her undergraduate thesis under Prof. Amy Vollmer studied E. coli with mutant Universal Stress Protein A variants. She used RNA microarrays to understand how their ethanol shock response was disrupted, segmenting the raw image files and analyzing the data in R herself. Emma entered the Chemical Biology PhD Program at Harvard University in 2013.

Publications

Mammalian Cells Engineered To Produce New Steroids
E Spady, T Wyche, N Rollins, J. Clardy, J Way, and P Silver. 9/2018. “Mammalian Cells Engineered To Produce New Steroids.” Chembiochem, 4, 19, Pp. 1827-1833. Publisher's VersionAbstract
Steroids can be difficult to modify through traditional organic synthesis methods, but many enzymes regio- and stereoselectively process a wide variety of steroid substrates. We tested whether steroid-modifying enzymes could make novel steroids from non-native substrates. Numerous genes encoding steroid-modifying enzymes, including some bacterial enzymes, were expressed in mammalian cells by transient transfection and found to be active. We made three unusual steroids by stable expression, in HEK293 cells, of the 7α-hydroxylase CYP7B1, which was selected because of its high native product yield. These cells made 7α,17α-dihydroxypregnenolone and 7β,17α-dihydroxypregnenolone from 17α-hydroxypregnenolone and produced 11α,16α-dihydroxyprogesterone from 16α-hydroxyprogesterone. The last two products were the result of CYP7B1-catalyzed hydroxylation at previously unobserved sites. A Rosetta docking model of CYP7B1 suggested that these substrates' D-ring hydroxy groups might prevent them from binding in the same way as the native substrates, bringing different carbon atoms close to the active ferryl oxygen atom. This new approach could potentially use other enzymes and substrates to produce many novel steroids for drug candidate testing.
G Despande, E Spady, J Goodhouse, and P Schedl. 11/2012. “Maintaining sufficient nanos is a critical function for polar granule component in the specification of primordial germ cells.” G3: Genes, Genomics, Genetics, 2, 11, Pp. 1397-1403. Publisher's VersionAbstract
Primordial germ cells (PGC) are the precursors of germline stem cells. In Drosophila, PGC specification is thought to require transcriptional quiescence and three genes, polar granule component (pgc), nanos (nos), and germ cell less (gcl) function to downregulate Pol II transcription. While it is not understood how nos or gcl represses transcription, pgc does so by inhibiting the transcription elongation factor b (P-TEFb), which is responsible for phosphorylating Ser2 residues in the heptad repeat of the C-terminal domain (CTD) of the largest Pol II subunit. In the studies reported here, we demonstrate that nos are a critical regulatory target of pgc. We show that a substantial fraction of the PGCs in pgc embryos have greatly reduced levels of Nos protein and exhibit phenotypes characteristic of nos PGCs. Lastly, restoring germ cell-specific expression of Nos is sufficient to ameliorate the pgc phenotype.

Curriculum Vitae