Damon Runyon Postdoctoral Fellowship (2016-2019)

The Basnet lab is broadly interested in understanding the molecular mechanisms of cancer metastasis using wide range of sequencing technologies and animal models of cancer. We have developed Flura-seq, which is a highly sensitive technique forin situtranscriptomics, to study the biology of underrepresented cell populations. We will extensively utilize Flura-seq, single cell sequencing (sc-Seq), ChIP-seq, ATAC-seq, RNA-seq and other relevant sequencing technologies in genetic mouse models of cancers along with patient-derived xenografts (PDXs) and cancer cell lines to address some of the most important clinically relevant questions in the field of cancer biology. More specifically, we are interested in:

1. Investigating the metabolic and immune selection pressure mounted by tissue microenvironment during early stages of cancer metastasis with an ultimate goal of developing targeted adjuvant therapies. Such an approach will allow us to devise treatment of metastatic cancers before they develop into life-threatening macrometastases.

2. Investigating crosstalk between immune cells and cancer cells. Immunotherapy has been proven to be very effective treatment for a subset of cancer patients, and a better understanding of the detailed crosstalk between cancer cells and immune cells is expected to identify new immunotherapies that could be effective to treat patients that are refractory to currently available immunotherapies like anti-PD1/PDL1 and anti-CTLA4 treatments.

Selected Publications:

1.Basnet H, Su XB, Tan Y, Meisenhelder J, Merkurjev D, Ohgi KA, Hunter T, Pillus L, Rosenfeld, MG. Tyrosine phosphorylation in Histone H2A by CK2 kinase regulates transcriptional elongation.Nature.516(7530): 267-71 (2014).

2.Basnet H, Tian L, Ganesh K, Huang Y, Macalinao DG, Brogi E, Finley L, Massague J. Flura-seq identifies organ- specific metabolic adaptations during early metastatic colonization.eLIFE.e43627(2019).

3.Basnet H, Massague J. Labeling and isolation of Fluorouracil tagged RNA by cytosine deaminaseexpression.Bio-protocol.9(22): e3433(2019).

4.Singh N*,Basnet H*, Wiltshire T, Mohammad DH, Thompson JR, Heroux A, Botuyan MV, Yaffe MB, Couch FJ, Rosenfeld MG, Mer G. Dual recognition of phosphoserine and phosphotyrosine in histone variant H2A.X byDNAdamage response protein MCPH1.PNAS. 109 (36): 14381-14386 (2012). (*equalcontribution)

5.Ganesh K,Basnet H, Laughney AM, Kaygusuz Y, He L, O’Rourke KP, Reuter V, Huang, Y, Er EE, Masilionis I, Weiser MR, Saltz LB, Garcia-Aguilar J, Koche R, Lowe SW, Pe’er D, Shia J, Massagué, J. L1CAM defines the regenerative origin of metastasis-initiating cells in colorectal cancer.Nat Cancer.(1): 28-45(2020).

6.Su Jie, Morgani SM, David CJ, Wang Q, Er EE, Huang Y,Basnet H, Zou Y, Shu W, Hendrickson RC, Soni RK, Hadjantonakis A, Massague J. Basis for EMT coupling to fibrogenic and developmental programs.Nature.577(7791): 566-571(2020).

7.Huang Y, Hu J, Chen F, Lecomte N,Basnet H, David CJ, Witkin PA, Leach SD, Iacobuzio-Donahue C, Massague J. ID1 mediates escape from TGFβ tumor suppression in pancreatic cancer.Cancer Discovery.10(1): 142-157(2019).

8.Malladi S, Macalinao DG, Jin X, He L,Basnet H, Zou Y, de Stanchina E, Massague J. Metastatic latency and immune evasion through autocrine inhibition of WNT.Cell. 165(1): 45-60(2016).

9.Wang J*, Telese F*, Tan Y*, Li W, Jin C, He X,Basnet H, Ma Q, Merkurjev D, Zhu X, Liu Z, Zhang J, Ohgi K, Taylor H, White RR, Tazearsalan C, Sun Y, Macfarlan TS, Pfaff SL, Rosenfeld MG. LSD1n is an H4K20 demethylase regulating memory formation via transcriptional elongation control.Nat Neurosci. 18(9): 1256-64 (2015). (*equalcontribution)

10.Tumaneng K,Schlegelmilch K, Russell R, Yimlamai D,Basnet H, Mahadevan N, Fitamant J, Bardeesy N, Camargo FD, Guan KL. YAP mediates crosstalk between the Hippo and PI3K-TOR pathways bysuppressing PTEN via miR-29.Nat Cell Biol. 14:1322-1329(2012)