James Dahlman
Assistant Professor, Biomedical Engineering | Georgia Tech College of Engineering
Atlanta, GA, UNITED STATES
James Dahlman uses molecular biology to rationally design the genetic drugs he delivers.
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Biography
James Dahlman is an Assistant Professor in the Georgia Tech BME Department. He studied RNA design and gene editing as a post-doc with Feng Zhang at the Broad Institute, and received his PhD from MIT and Harvard Medical School in 2014, where he studied RNA delivery with Robert Langer and Daniel Anderson.
The Lab for Precision Therapies at Georgia Tech, also called the 'Dahlman Lab', works at the interface of drug delivery, nanotechnology, genomics, and gene editing. James has designed nanoparticles that deliver RNAs to the lung and heart; these nanoparticles have been used by over ten labs across the US to date. He has also developed targeted in vivo combination therapies; nanoparticles deliver multiple therapeutic RNAs at once, in order to manipulate several nodes on a single disease pathway. More recently, he developed a method to quantify the targeting, biodistribution, and pharmacokinetics of dozens to hundreds of distinct nanoparticles at once directly in vivo.
Finally, James uses molecular biology to rationally design the genetic drugs he delivers. He recently reported 'dead' guide RNAs; these engineered RNAs can be used to simultaneously up- and down-regulate different genes in a single cell using Cas9.
James has won the NSF, NDSEG, NIH OxCam, Whitaker Graduate, and LSRF Fellowships, the Weintraub Graduate Thesis Award, and was recently named a Bayer Young Investigator and Parkinson's Disease Foundation Young Investigator. He has had significant help along the way. Besides having great scientific advisors, James has been lucky to mentor excellent students, including two that were finalists for the Rhodes Scholarship.
Areas of Expertise (8)
Vascular and Immunoengineering
DNA Barcoded Nanoparticles
Drug Delivery
CRISPR
Gene Editing
Cas9
RNA Therapies
Big Data / Nanotechnology
Selected Accomplishments (2)
Young Innovator
2019 Cellular and Molecular Bioengineering
Emerging Investigator
2018 Named an emerging investigator in chemistry / materials science by the Journal of Materials Chemistry B
Education (2)
MIT: Ph.D., Medical Engineering 2014
Wright State University: B.S., Biomedical Engineering 2009
Links (6)
Selected Media Appearances (5)
DNA Data Storage Is Closer Than You Think
Scientific American online
2019-07-01
Every minute in 2018, Google conducted 3.88 million searches, and people watched 4.33 million videos on YouTube, sent 159,362,760 e-mails, tweeted 473,000 times and posted 49,000 photos on Instagram, according to software company Domo. By 2020 an estimated 1.7 megabytes of data will be created per second per person globally, which translates to about 418 zettabytes in a single year (418 billion one-terabyte hard drive’s worth of information), assuming a world population of 7.8 billion. The magnetic or optical data-storage systems that currently hold this volume of 0s and 1s typically cannot last for more than a century, if that. Further, running data centers takes huge amounts of energy. In short, we are about to have a serious data-storage problem that will only become more severe over time.
Red Glow Helps Identify Nanoparticles for Delivering RNA Therapies
Georgia Tech News Center online
2018-10-01
A new screening process could dramatically accelerate the identification of nanoparticles suitable for delivering therapeutic RNA into living cells. The technique would allow researchers to screen hundreds of nanoparticles at a time, identifying the organs in which they accumulate – and verifying that they can successfully deliver an RNA cargo into living cells.
MIT Technology Review Applauds Georgia Tech’s Dahlman in ‘35 Innovators Under 35’
Georgia Institute of Technology online
2018-07-02
When a recognition makes your name fit comfortably into the same sentence with Facebook’s “Mark Zuckerberg” or Google co-founder “Larry Page,” you know it’s something special. A shout-out in the MIT Technology Review’s annual roster of “35 Innovators Under 35” did just that for Georgia Tech biomedical researcher James Dahlman.
$21.9 Million Gene Modulation Research Effort Targets Influenza Pandemics
Georgia Tech News Center online
2019-06-28
A multifaceted research effort aimed at temporarily modulating gene expression using RNA-based techniques could help protect against pandemic flu by boosting lung resistance to infection, attacking the influenza virus directly, enhancing immune system response and improving the effects of existing vaccines.
Comparison Shows Value of DNA Barcoding in Selecting Nanoparticles
Georgia Tech News Center online
2018-03-05
The first direct comparison of in vitro and in vivo screening techniques for identifying nanoparticles that may be used to transport therapeutic molecules into cells shows that testing in lab dishes isn’t much help in predicting which nanoparticles will successfully enter the cells of living animals.
Patents (2)
Novel crispr enzymes and systems
US20190233814A1
2019-08-21
The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA or RNA-targeting systems comprising a novel DNA or RNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA.
Conjugated lipomers and uses thereof
US20190167795A1
2019-06-06
wherein R3 and R4 are as defined herein. Also provided are compositions comprising the inventive conjugated lipomers, and methods of preparation and use.
Selected Articles (5)
Ligand Conjugated Multimeric siRNAs Enable Enhanced Uptake and Multiplexed Gene Silencing
Nucleic Acid TherapeuticsJonathan M. Brown, James E. Dahlman, Kristin K. Neuman, Carla A.H. Prata, Monika C. Krampert, Philipp M. Hadwiger, and Hans-Peter Vornlocher
2019 Small interfering RNAs (siRNAs) conjugated to N-acetylgalactosamine (GalNAc) ligands have been used to treat disease in patients. However, conjugates with other ligands deliver siRNA less efficiently, limiting the development of new targeted therapies. Most approaches to enhancing the potency of such conjugates have concentrated on increasing ligand effectiveness and/or the chemical stability of the siRNA drug. One complementary and unexplored alternative is to increase the number of siRNAs delivered per ligand. An ideal system would be a single chemical entity capable of delivering multiple copies of an oligonucleotide drug and/or several such drugs simultaneously. Here we report that siRNAs can be stably linked together under neutral aqueous conditions to form chemically defined siRNA “multimers,” and that these multimers can be delivered in vivo by a GalNAc ligand. Conjugates containing multiple copies of the same siRNA showed enhanced activity per unit of ligand, whereas siRNAs targeting different genes linked to a single ligand facilitated multigene silencing in vivo; this is the first demonstration of silencing several genes simultaneously in vivo using ligand-directed multimeric siRNA. Multimeric oligonucleotides represent a powerful and practical new approach to improve intracellular conjugate delivery.
BOLA (BolA Family Member 3) Deficiency Controls Endothelial Metabolism and Glycine Homeostasis in Pulmonary Hypertension
CirculationQiujun Yu, Yi-Yin Tai, Ying Tang, Jingsi Zhao, Vinny Negi, Miranda K Culley, Jyotsna Pilli, Wei Sun, Karin Brugger, Johannes Mayr, Rajeev Saggar, Rajan Saggar, W Dean Wallace, David J Ross, Aaron B Waxman, Stacy G Wendell, Steven J Mullett, John Sembrat, Mauricio Rojas, Omar F Khan, James E Dahlman, Masataka Sugahara, Nobuyuki Kagiyama, Taijyu Satoh, Manling Zhang, Ning Feng, John Gorcsan III, Sara O Vargas, Kathleen J Haley, Rahul Kumar, Brian B Graham, Robert Langer, Daniel G Anderson, Bing Wang, Sruti Shiva, Thomas Bertero, Stephen Y Chan
2019 Deficiencies of iron-sulfur (Fe-S) clusters, metal complexes that control redox state and mitochondrial metabolism, have been linked to pulmonary hypertension (PH), a deadly vascular disease with poorly defined molecular origins. BOLA3 (BolA Family Member 3) regulates Fe-S biogenesis, and mutations in BOLA3 result in multiple mitochondrial dysfunction syndrome, a fatal disorder associated with PH. The mechanistic role of BOLA3 in PH remains undefined.
Nanoparticles Containing Oxidized Cholesterol Deliver mRNA to the Liver Microenvironment at Clinically Relevant Doses
Advanced MaterialsKalina Paunovska, Alejandro J Da Silva Sanchez, Cory D Sago, Zubao Gan, Melissa P Lokugamage, Fatima Z Islam, Sujay Kalathoor, Brandon R Krupczak, James E Dahlman
2019 Using mRNA to produce therapeutic proteins is a promising approach to treat genetic diseases. However, systemically delivering mRNA to cell types besides hepatocytes remains challenging. Fast identification of nanoparticle delivery (FIND) is a DNA barcode‐based system designed to measure how over 100 lipid nanoparticles (LNPs) deliver mRNA that functions in the cytoplasm of target cells in a single mouse. By using FIND to quantify how 75 chemically distinct LNPs delivered mRNA to 28 cell types in vivo, it is found that an LNP formulated with oxidized cholesterol and no targeting ligand delivers Cre mRNA, which edits DNA in hepatic endothelial cells and Kupffer cells at 0.05 mg kg−1. Notably, the LNP targets liver microenvironmental cells fivefold more potently than hepatocytes. The structure of the oxidized cholesterols added to the LNP is systematically varied to show that the position of the oxidative modification may be important; cholesterols modified on the hydrocarbon tail associated with sterol ring D tend to outperform cholesterols modified on sterol ring B. These data suggest that LNPs formulated with modified cholesterols can deliver gene‐editing mRNA to the liver microenvironment at clinically relevant doses.
CRISPR-Cas9 Knockin Mice for Genome Editing and Cancer Modeling
CellRandall J Platt, Sidi Chen, Yang Zhou, Michael J Yim, Lukasz Swiech, Hannah R Kempton, James E Dahlman, Oren Parnas, Thomas M Eisenhaure, Marko Jovanovic, Daniel B Graham, Siddharth Jhunjhunwala, Matthias Heidenreich, Ramnik J Xavier, Robert Langer, Daniel G Anderson, Nir Hacohen, Aviv Regev, Guoping Feng, Phillip A Sharp, Feng Zhang
2014 CRISPR-Cas9 is a versatile genome editing technology for studying the functions of genetic elements. To broadly enable the application of Cas9 in vivo, we established a Cre-dependent Cas9 knockin mouse. We demonstrated in vivo as well as ex vivo genome editing using adeno-associated virus (AAV)-, lentivirus-, or particle-mediated delivery of guide RNA in neurons, immune cells, and endothelial cells. Using these mice, we simultaneously modeled the dynamics of KRAS, p53, and LKB1, the top three significantly mutated genes in lung adenocarcinoma. Delivery of a single AAV vector in the lung generated loss-of-function mutations in p53 and Lkb1, as well as homology-directed repair-mediated KrasG12D mutations, leading to macroscopic tumors of adenocarcinoma pathology. Together, these results suggest that Cas9 mice empower a wide range of biological and disease modeling applications.
Treating Metastatic Cancer With Nanotechnology
Nature Reviews CancerAvi Schroeder, Daniel A Heller, Monte M Winslow, James E Dahlman, George W Pratt, Robert Langer, Tyler Jacks, Daniel G Anderson
2012 Metastasis accounts for the vast majority of cancer deaths. The unique challenges for treating metastases include their small size, high multiplicity and dispersion to diverse organ environments. Nanoparticles have many potential benefits for diagnosing and treating metastatic cancer, including the ability to transport complex molecular cargoes to the major sites of metastasis, such as the lungs, liver and lymph nodes, as well as targeting to specific cell populations within these organs. This Review highlights the research, opportunities and challenges for integrating engineering sciences with cancer biology and medicine to develop nanotechnology-based tools for treating metastatic disease.
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