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Nikki K. Lytle
University of California, San Diego
Pancreatic cancerStem cellCancer researchCancer stem cellBiology
15Publications
9H-index
238Citations
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Publications 19
Newest
#1Yao-Cheng Li (Salk Institute for Biological Studies)H-Index: 6
#2Nikki K. Lytle (Salk Institute for Biological Studies)H-Index: 9
Last. Frank McCormick (UCSF: University of California, San Francisco)H-Index: 115
view all 11 authors...
HRAS, NRAS, and KRAS4A/KRAS4B comprise the RAS family of small GTPases that regulate signaling pathways controlling cell proliferation, differentiation, and survival. RAS pathway abnormalities cause developmental disorders and cancers. We found that KRAS4B colocalizes on the cell membrane with other RAS isoforms and a subset of prenylated small GTPase family members using a live-cell quantitative split luciferase complementation assay. RAS protein coclustering is mainly mediated by membrane asso...
Source
#1Simone Bersini (Salk Institute for Biological Studies)H-Index: 1
#2Nikki K. Lytle (Salk Institute for Biological Studies)H-Index: 9
Last. Martin W. Hetzer (Salk Institute for Biological Studies)H-Index: 47
view all 6 authors...
Nucleoporin 93 (Nup93) expression inversely correlates with the survival of triple-negative breast cancer patients. However, our knowledge of Nup93 function in breast cancer besides its role as structural component of the nuclear pore complex is not understood. Combination of functional assays and genetic analyses suggested that chromatin interaction of Nup93 partially modulates the expression of genes associated with actin cytoskeleton remodeling and epithelial to mesenchymal transition, result...
1 CitationsSource
#1Kathleen E. DelGiorno (Salk Institute for Biological Studies)H-Index: 2
#2Chi-Yeh Chung (Salk Institute for Biological Studies)H-Index: 1
Last. Geoffrey M. Wahl (Salk Institute for Biological Studies)H-Index: 74
view all 25 authors...
Despite numerous advances in our understanding of pancreatic ductal adenocarcinoma (PDA) genetics and biology, this disease is expected to become the second leading cause of cancer-related U.S. deaths within the next few years. Incomplete understanding of how it arises precludes development of early detection and interception strategies to improve therapeutic outcomes. Acinar-ductal metaplasia involving genesis of tuft cells is one early step in PDA formation, but their functional significance h...
Source
#1Lesley Paige Ferguson (UCSD: University of California, San Diego)
#2Jovylyn Gatchalian (Salk Institute for Biological Studies)H-Index: 2
Last. Tannishtha Reya (UCSD: University of California, San Diego)H-Index: 32
view all 12 authors...
Pancreatic adenocarcinoma (PDAC) is a devastating disease characterized by high rates of metastasis and poor therapeutic response. It is currently the 4th leading cause of cancer-related deaths in developed countries, and despite efforts to improve therapy, the five-year survival rate remains at 9%. Therefore, it is critical to identify new programs that drive pancreatic cancer progression and therapeutic resistance. To define new cancer dependencies, work in the Reya lab has focused on characte...
Source
#1Nikki K. Lytle (UCSD: University of California, San Diego)H-Index: 9
#2L. Paige Ferguson (UCSD: University of California, San Diego)H-Index: 1
Last. Tannishtha ReyaH-Index: 32
view all 33 authors...
Summary Drug resistance and relapse remain key challenges in pancreatic cancer. Here, we have used RNA sequencing (RNA-seq), chromatin immunoprecipitation (ChIP)-seq, and genome-wide CRISPR analysis to map the molecular dependencies of pancreatic cancer stem cells, highly therapy-resistant cells that preferentially drive tumorigenesis and progression. This integrated genomic approach revealed an unexpected utilization of immuno-regulatory signals by pancreatic cancer epithelial cells. In particu...
7 CitationsSource
#1Yu Shi (Salk Institute for Biological Studies)H-Index: 7
#2Weina Gao (SU: Southern University and A&M College)H-Index: 2
Last. Tony Hunter (Salk Institute for Biological Studies)H-Index: 155
view all 38 authors...
Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis largely owing to inefficient diagnosis and tenacious drug resistance. Activation of pancreatic stellate cells (PSCs) and consequent development of dense stroma are prominent features accounting for this aggressive biology1,2. The reciprocal interplay between PSCs and pancreatic cancer cells (PCCs) not only enhances tumour progression and metastasis but also sustains their own activation, facilitating a vicious cycle to exacerbate tum...
11 CitationsSource
#1Kyle Spinler (UCSD: University of California, San Diego)
#2Tannishtha Reya (UCSD: University of California, San Diego)H-Index: 32
Last. Jeffrey D. Esko (UCSD: University of California, San Diego)H-Index: 77
view all 14 authors...
Source
#1Nikki K. Lytle (UCLA: University of California, Los Angeles)H-Index: 9
#2Alison G. Barber (UCLA: University of California, Los Angeles)H-Index: 1
Last. Tannishtha Reya (UCLA: University of California, Los Angeles)H-Index: 32
view all 3 authors...
Although we have come a long way in our understanding of the signals that drive cancer growth, and how these signals can be targeted, effective control of this disease remains a key scientific and medical challenge. The therapy resistance and relapse that are commonly seen are driven in large part by the inherent heterogeneity within cancers that allows drugs to effectively eliminate some, but not all, malignant cells. Here, we focus on the fundamental drivers of this heterogeneity by examining ...
26 CitationsSource
#1Christopher Dravis (Salk Institute for Biological Studies)H-Index: 13
#2Chi-Yeh Chung (Salk Institute for Biological Studies)H-Index: 1
Last. Geoffrey M. Wahl (Salk Institute for Biological Studies)H-Index: 74
view all 8 authors...
Summary Cell state reprogramming during tumor progression complicates accurate diagnosis, compromises therapeutic effectiveness, and fuels metastatic dissemination. We used chromatin accessibility assays and transcriptional profiling during mammary development as an agnostic approach to identify factors that mediate cancer cell state interconversions. We show that fetal and adult basal cells share epigenetic features consistent with multi-lineage differentiation potential. We find that DNA-bindi...
14 CitationsSource
#1Jelena Todoric (UCSD: University of California, San Diego)H-Index: 17
#2Laura Antonucci (UCSD: University of California, San Diego)H-Index: 6
Last. Michael Karin (UCSD: University of California, San Diego)H-Index: 215
view all 19 authors...
Summary Despite expression of oncogenic KRAS , premalignant pancreatic intraepithelial neoplasia 1 (PanIN1) lesions rarely become fully malignant pancreatic ductal adenocarcinoma (PDAC). The molecular mechanisms through which established risk factors, such as chronic pancreatitis, acinar cell damage, and/or defective autophagy increase the likelihood of PDAC development are poorly understood. We show that accumulation of the autophagy substrate p62/SQSTM1 in stressed Kras G12D acinar cells is as...
22 CitationsSource
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