The Lo Lab studies therapeutic resistance in metastatic melanoma in order to build rationales for clinical trials and to develop novel treatment combinations or treatment regimens. In our studies of cancer resistance, we focus on foundational therapies (i.e., MAPK pathway- and immune checkpoint-targeted therapies) that are highly active against advanced melanoma but whose long-term clinical or survival impacts are still limited by difference forms of resistance (innate, adaptive, acquired). Findings from our work have served as key rationales for several clinical trials, including the successful development of BRAF and MEK inhibitor combo.
We use high-throughput technologies (whole-exome sequencing, RNA-seq, methylome arrays, scRNA-seq, CyTOF, etc.) to dissect melanoma biology in the context of clinical and experimental resistance. We also use traditional cell biological and biochemical approaches to dissect two major cancer pathways, i.e., the MAPK and the PD-1/PD-L1 or -L2 pathways. Below are examples of on-going projects:
1) Resistance to MEK inhibitors across melanoma sub-types and the development of novel RAF inhibitors to overcome MAPK-reactivation-driven resistance.
2) Optimal sequencing regimen using MAPK and PD-1 targeted therapies and the molecular basis for sequencing regimens.
3) Organ site-specific factors that drive melanoma metastasis and resistance to current foundational therapies. We are analyzing tumor and adjacent normal organ tissues from warm autopsies. We are also analyzing experimental metastasis of murine and human melanoma.
4) The use of PARP inhibitors in the context of melanoma with acquired resistance to MAPK inhibitors. MAPK inhibitor-resistant melanoma are “addicted” to MAPK inhibitors and, when withdrawn from the MAPK inhibitor(s), can undergo cell death when further challenged with PARP inhibitors.
5) Regulation of post-transcriptional and -translational cell-surface levels of PD-L1 and PD-L2 in cancer and the tumor microenvironment. Alterations in these processes have been implicated in acquired resistance to anti-PD-1 therapy.
6) Combination therapies that overcome innate anti-PD-1 resistance.
7) Pan-cancer therapeutic approaches inspired by recent therapeutic developments against melanoma. We are particularly interested in human malignancies driven by RAS mutations.
We have two postdoctoral fellowships available in the Lo Laboratory, focused on melanoma research and bioinformatics.
This postdoctoral position is focused on melanoma research toward our understanding of the mechanisms of acquired resistance to targeted therapies (B-RAF inhibitors) using integrated genomics. We are affiliated with the Department of Medicine/Division of Dermatology, the Department of Molecular and Medical Pharmacology, and the Jonsson Comprehensive Cancer Center (Tumor Cell Biology Program) at the University of California, Los Angeles.
The ideal candidate must have extensive experience handling RNA, DNA and protein. His or her skill set should include:
Interested individuals should have:
This position is available immediately in the Lo Laboratory, which is focused on melanoma research in the following thematic areas:
We are affiliated with the following departments at UCLA:
The ideal candidates must have experience with:
Interested individuals should have:
Interested individuals should forward a CV along with three letters of recommendation, one from the doctoral thesis advisor or current employer, to rlo@mednet.ucla.edu.
