안녕하세요.  NanoBiomedical Research(KBLEE Group) 이기범입니다. 

저는 2008년부터 미국 뉴저지 주립대학교인 Rutgers University의 Chemistry and Chemical Biology학과에서 교수로 재직 중이며, 현재 석좌교수직을 맡고 있습니다. Rutgers University는 한국에서는 다소 생소할 수 있지만, 뉴저지 주에서 가장 큰 주립대학 중의 하나로 주 정부의 전폭적인 지원을 받고 있습니다. 뉴저지 주는 뉴욕과 펜실베니아 사이에 위치하고 있으며, 한국인을 포함한 다양한 아시아계 및 여러 인종이 조화롭게 거주하고 있는 곳입니다. Rutgers University는 뉴저지 주 내에서 Princeton University와 함께 연구 중심 대학(Doctoral Universities–Very high researchactivity, R1 Group)으로 분류되며, Harvard University, Columbia University 등 미국 동부의 유수한 대학 및 연구 기관과 활발한 공동 연구를 수행하고 있습니다.

저희 연구팀은 나노기술과 화학생물학의 융합을 통해 암세포와 줄기세포의 신호전달 경로를 조절하는 혁신적인 방법론을 개발하는 데 주력하고 있습니다. 특히, 줄기세포와 암세포의 운명을 결정짓는 다양한 미세환경 신호를 규명하는 데 초점을 맞추고 있습니다. 이를 통해 줄기세포의 분화를 촉진하고 암세포의 사멸을 유도하는 새로운 전략을 모색하고자 합니다. 또한, 저희 연구팀은 암 치료, 분자 영상, 바이오 센싱 등 다양한 분야에 응용 가능한 혁신적인 나노 소재 개발에도 힘쓰고 있습니다. 이러한 나노 소재들은 암 진단 및 치료 분야에 패러다임 시프트를 일으킬 수 있을 것으로 기대하고 있습니다.

현재 저희 연구팀은 줄기세포 또는 암세포와 미세환경 간의 복잡한 상호작용을 심도 있게 이해하기 위해 다양한 분야에서 연구를 진행하고 있습니다. 앞으로도 나노기술과 화학생물학의 경계를 넘나드는 창의적인 연구를 통해 인류 건강에 기여할 수 있는 혁신적인 성과를 이루어 내고자 최선을 다하고 있습니다.

Ki Bum Lee, Ph.D. (이기범)
Distinguished Professor, Department of Chemistry and Chemical Biology, Rutgers University

Ecucation & Experiences 
2008 - Present  Department of Chemistry and Chemical Biology, Rutgers University
Rutgersfaculty in the following Programs, Depts, and Institutes: Biomedical Engineering,Chemical & Biochemical Engineering, Molecular Biosciences, Rutgers Stem Cell Research Center,Human Genetics Institute of New Jersey, Rutgers Brain Health Institute, Quantitative BiomedicineGraduate Program, Cancer Institute of New Jersey

2007 Postdoc The Scripps Research Institute
2004  Ph.D.  Department of Chemistry, Northwestern University 

Long-Term Research Goals and Vision Statement:

Our group's research focuses on developing innovative methods that integrate nanotechnology and chemical biology to control stem cell and cancer cell fate by modulating their microenvironment. We aim to understandand manipulate the complex interactions between cells and their surroundings, including soluble cues, cell-cellinteractions, and insoluble/physical cues. [Fig.1]

Figure 1. Schematic diagram of our nanotechnology-based approaches for the regulation ofcancer/stem cell fate via three different kinds of microenvironmental cues in disease andinjury conditions.

Our primary goal is to developtransformative tools to enhancestem cell differentiation andcancer cell apoptosisin vitro,exvivo, andin vivo. We focus onneurodegenerative diseases andcentral nervous system (CNS)injuries, where themicroenvironment differssignificantly from normalconditions. To address thechallenges in current stem celltherapies, we have developedfourinnovative methods : 

 1.Multifunctional Nanomaterials as a Toolkit to Control Cancer and Stem Cells Fate

 2.A nonviral genetic manipulation method mimicking natural transcription factors.

 3.A multifunctional nanomaterial-based bioscaffold for controlled therapeutic molecule delivery.

 4.A nanomaterial-based bioscaffold to enhance stem cell transplantation.

Our research aims to establish advanced nanotechnology tools as a new platform for gene manipulation andstem cell-based tissue engineering. This will ultimately leadto effective cellular reprogramming, cell replacementtherapies, and safe gene therapy for patients suffering from CNS injuries and neurodegenerative diseases.

Synthesizing and Developing a New Generation of Multifunctional Nanomaterials as a Toolkit to Control Cancer and Stem Cells Fate

Figure 2. A library of multifunctional nanoparticles which have been developed by KBLEEgroup for bio-applications.

Development of a Nanoparticle-based Artificial Transcription Factor (NanoScript) for Effective Gene Regulation in Cellular Reprogramming

Transcription factors (TFs), which are proteins regulating cell function and behavior, are routinely delivered into stem cells or somatic cells using conventional methods such as viruses or plasmids, which pose several safety concerns, including random DNA integration and formation of cancerous teratomas. Hence, stem cell-based therapies cannot be effectively translated into the clinic to treat patients. As an alternative approach to regulate gene expression for stem cell differentiation, recent efforts have focused on developing a class of small molecules called synthetic transcription factors (STFs), which are small molecules that can mimic the function of TFs. Even though STFs have been demonstrated to activate genes in a non-viral manner, translating them for stem cell differentiation or clinical application has proven difficult due to poor membrane permeability, propensity for intracellular degradation, and inadequate nuclear targeting.

Figure 3. Schematic diagram of NanoScript

NanoScript replicates the multi-domain structure of TF proteins by tethering three major components,representing the primary domains [nuclear localization signal (NLS) domain, DNA-binding domain (DBD), andactivation domain (AD)] found on endogenous TFs, in close proximity on a single gold nanoparticle (AuNP). Inaddition to serving as a delivery vehicle for STFs, the AuNP itself functions as a component of the NanoScript,mimicking the linker domain (LD) of natural TF proteins. NanoScript emulates the gene-regulating function ofTFs by translocating into the nucleus, binding specifically to DNA, and recruiting transcriptional machinery toeither upregulate or repress genes of interest

Combinatorial Nanomaterial-Based Approaches to generate Stem Cell-based Neural Networks and Detect Neurotransmitters in Stem Cell-derived Neural Interface

The search for novel ways to explore and better understand the functions of insoluble/physical cues on the behaviors of stem cells is vital in the areas of regenerative medicine, as the insoluble/physical microenvironmental signals significantly affect the behaviors of cells, including stem cell adhesion, growth, migration, and differentiation. In this context, stem cells can sense and consequently respond to the physical microenvironment in which they reside. For instance, changes in cell shape and alignment are vital cellular responses to surface properties of the underlying substrate. Several approaches based on surface chemistry and nano/microfabrication have been examined over the last decade to comprehend these phenomena. However, establishing controlled and reliable methodologies to guide stem cell differentiation into specialized cell lineages via modulating insoluble/physical cues remains to be achieved. To address the aforementioned challenges, we have focused on two overarching strategies to control this process selectively. In our first approach, we modulated the surface chemistry of 2D substrates to control neural stem cell morphology and the resulting differentiation process. Patterned surfaces, consisting of immobilized extracellular matrix proteins and/or nanomaterials, were generated and observed to guide neuronal differentiation and polarization. Building on the abovementioned approaches, we further tuned the cell-substrate interactions in a third approach by introducing nanotopographical features in the form of nanoparticle films and nanofibers. Besides providing a 3D surface topography, our unique nano-scaffolds were observed to enhance gene delivery, facilitate axonal alignment, selectively control differentiation into neural cell lines of interest, and generate stem cell-based neural interfaces.

See more detailed

Advanced Stem Cell Therapies for CNS injuries and Advanced in vivo Drug/Gene Delivery using Bioinspired Hybrid Nanoscaffolds

Central nervous system (CNS) injuries [e.g., spinal cord injury (SCI) and traumatic brain injury (TBI)] result in many cellular dysfunctions that may cause severe and permanent neurological deficits. Several current therapeutic approaches aim to bridge the lesion site through cellular transplantation to restore neural signaling, reduce inflammation, and prevent subsequent damage to the injured area. Given the intrinsically limited regenerative potential of the central nervous system (CNS) and the complex inhibitory environment of the injured spinal cord, effective strategies to generate a robust population of functional neurons derived from autologous stem cells [induced pluripotent stem cells (iPSCs) and neural stem cells (NSCs)] re-establishing the damaged neural circuitry are urgent clinical needs. However, several pertinent obstacles hinder successful transplantation strategies. First, due to the inflammatory nature of the injured spinal cord, most NSCs die soon after transplantation. Second, the extracellular matrix of the injured spinal cord is not very conducive to NSC survival and differentiation. Thus, we will address these challenges by combining a novel bioscaffold with therapeutic molecules (e.g., small molecules, biologics, genetic materials-RNAs/DNAs) to reduce inflammation and promote neuronal differentiation.

See more detailed

[최근 4년, 2021~ ] 

BRIC 한빛사논문 : 이기범 

1. Enhancing CAR Macrophage Efferocytosis via Surface Engineered Lipid Nanoparticles Targeting LXR Signaling", Advanced Materials, 2024, Accepted. doi.org/10.1002/adma.202308377
2. 
   
3. 
   
4. "Magnetic Nanoparticle-Assisted Non-Viral CRISPR-Cas9 for Enhanced Genome Editing to Treat Rett Syndrome ", Advanced Science, 2024, Accepted.
5. 
   
6. 
   
7. "Real-Time, Non-Invasive Monitoring of Neuronal Differentiation Using Intein-Enabled Fluorescence Signal Translocation in Genetically Encoded Stem Cell-Based Biosensors",", Advanced Functional Materials, 2024, Accepted. doi.org/10.1002/adfm.202400394
8. 
   
9. 
   
10. "Enhanced Intervertebral Disc Repair and Regeneration Using a Nano-Hybrid Peptide Hydrogel", ACS Nano, 2023, 17, 4, 3750-3764.  doi.org/10.1021/acsnano.2c11441
11. 
    
12. 
    
13. "In Situ Detection of Neuroinflammation using Multi-cellular 3D Neurovascular Unit-on-a-Chip", Advanced Functional Materials, 2023, Accepted. 

• 
  
• 
  
• "Effective Modulation of Inflammation and Oxidative Stress for Enhanced Regeneration of Intervertebral Discs Using 3D Porous Hybrid Protein Nanoscaffold", Advanced Materials, 2023, 2303021,  DOI: doi.org/10.1002/adma.202303021
• 
  
• 
  
• “Nanotechnology Approaches to Investigate Chemotherapy-Induced Neurotoxicity, Neuropathy, and Cardiomyopathy in Breast and Ovarian Cancer Survivors”, Small, 2023, 2300744. DOI:doi.org/10.1002/smll.202300744
• 
  
• 
  
• “Commentary on Different Ways to Die: Cell Death Mechanisms and Their Association With Spinal Cord Injury”, Neurospine, 2023, 20, 2, 449-450.
• 
  
• 
  
• "In Situ Photoswitchable Cation-π Interactions in Ligand Self-Assembly for Stem Cell   Regulation In Vivo", Bioactive Materials, 2023, Accepted. 
• 
  
• 
  
• “MitoScript: A Nanoparticle-based Effective Mitochondrial DNA Transcription Regulator”, Nano Letters, 2023, DOI:10.1021/acs.nanolett.2c03958 Highlighted and selected as (the Cover in Nano Letters)
• 
  
• 
  
• "Injectable BIOorthogonal HydroGEL (BIOGEL) Accelerates Tissue Regeneration in Degenerated Intervertebral Discs", Bioactive Materials, 2023, 23, 562. 
• 
  
• 
  
• “Advanced Theragnostics for the Central Nervous System (CNS) and Neurological Disorders Using Functional Inorganic Nanomaterials”, Advanced Drug Delivery Reviews, 2023, 192, 114636. 
• 
  
• 
  
• “The effect of Nano- liposomal sodium nitrite on smooth muscle cell growth in a tissue- engineered small- diameter vascular graft”, Artificial Organs, 2023, 47, 1104. 
• 
  
• 
  
• "Advanced Drug Delivery Via Hybrid Nanofibers Enhance Stem Cell Differentiation", ACS Applied Materials & Interfaces, 2022, 14, 34488-34501. 
• 
  
• 
  
• “High-Content Screening And Analysis of Stem Cell-Derived Neural Interfaces Using Combinatorial Nanotechnology Approach and An Integrated Machine Learning”, Research, 2022:1-15, DOI:10.34133/2022/9784273
• 
  
• 
  
• "Predictive Biophysical Cue Mapping for Cellular Differentiation and Reprogramming Using Combinatorial Nanoarrays", ACS Nano, 2022,  18, 5577-5586.
• 
  
• 
  
• “Ultrasensitive Electrochemical Detection of Mutated Viral RNAs with Single Nucleotide Resolution Using a Nanoporous Electrode Array (NPEA)”, ACS Nano, 2022, 16, 5764-5777.

1. 
   
2. 
   
3. “Harnessing the Therapeutic Potential of Extracellular Vesicles for Biomedical Applications using Multifunctional Magnetic Nanomaterials", Small, 2022, 18, 2104783.  Highlighted and selected as (the Cover in Small)
4. 
   
5. 
   
6. "Injectable hybrid inorganic nanoscaffold as rapid stem cell assembly template for cartilage repair", National Science Review, 2022, 9: nwac037, https://doi.org/10.1093/nsr/nwac037 
7. 
   
8. 
   
9. "Nanotechnology‑enabled immunoengineering approaches to advance therapeutic applications", Nanoconvergence, 2022, 9, 19. 
10. 
    
11. 
    
12. “Acoustic Force Spectroscopy Reveals Subtle Differences in Cellulose Unbinding Behavior of Carbohydrate-Binding Modules", Proc. Natl. Acad. Sci., 2022, 119 (42) e2117467119. https://doi.org/10.1073/pnas.2117467119
13. 
    
14. 
    
15. “Structurally Defined Water-Soluble Metallofullerene Derivatives towards Biomedical Applications”, Angew. Chem. Int. Ed., 2022, https://doi.org/10.1002/anie.202211704
16. 
    
17. 
    
18. “Photoswitchable Microgel for Dynamic Macrophage Modulation", Advanced Materials, 2022, 2205498, DOI: 10.1002/adma.202205498
19. 
    
20. 
    
21. "Investigation of Electrical Stimulation on Phenotypic Vascular Smooth Muscle Cells Differentiation in Tissue-Engineered Small-Diameter Vascular Graft", Tissue and Cell, 2022, 81, 101996.
22. 
    
23. 
    
24. "A novel coculture assay to evaluate the effects of sympathetic innervation on vascular smooth muscle differentiation", Bioorganic Chemistry, 2022, 133, 106233.
25. 
    
26. 
    
27. “Manipulating Nanoparticle Aggregates Regulates Receptor-Ligand Binding in Macrophages", J. Am. Chem. Soc., 2022, 144, 5769-5783.
28. 
    
29. 
    
30. “Manipulating Nanoparticle Aggregates Regulates Receptor-Ligand Binding in Macrophages", J. Am. Chem. Soc., 2022, 144, 5769-5783.
31. 
    
32. 
    
33. “Submolecular Tuning of Ligand Size and Spacing for Dynamic Macrophage Modulation", Advanced Materials, 2022, 34, 2110340.
34. 
    
35. 
    
36. "Evaluation of Antibacterial and Mechanical Features of Dental Adhesives Containing Colloidal Gold Nanoparticles", Journal of Molecular Liquids, 2022, 365, 119824.
37. 
    
38. 
    
39. "A Review of 3D Printing Technology for Rapid Medical Diagnostic Tools", Molecular Systems Design & Engineering, 2022, 7, 315-324.
40. 
    
41. 
    
42. “Receptor-Level Proximity and Fastening of Ligands Mediates Stem Cell Differentiation", Advanced Functional Materials, 2022, 32, 2200828.
43. 
    
44. 
    
45. "Hybrid SMART Spheroids for Enhanced Stem Cell-based Cell Replacement Therapy ", Science Advances, 2021, 7, 40, DOI: 10.1126/sciadv.abj2281
46. 
    
47. 
    
48. "Bioengineering Approaches for the Advanced Organoid Research", Advanced Materials, 2021, 2007949, 33, 2007949.
49. 
    
50. 
    
51. “Biomolecular electron controller composed of nanobiohybrid with electrically released complex for spatiotemporal control of neuronal differentiation”, Small Method, 2021, 6, 2100912.
52. 
    
53. 
    
54. “Clustered Regularly Interspaced Short Palindromic Repeats-Mediated Amplification-Free Detection of Viral DNAs Using Surface-Enhanced Raman Spectroscopy-Active Nanoarray”, ACS Nano, 2021, 15, 8, 13475-13485.
55. 
    
56. 
    
57. “Magnetic Control of the Vertical Position of Hierarchic Ligand Nanoassembly Regulates the Mechanosensing-Mediated Differentiation of Stem Cells", Small, 2021, 17, 2102892. 
58. 
    
59. 
    
60. "Remote Switching of Elastic Movement of Decorated Ligand Nanostructures Controls the Adhesion-Regulated Polarization of Host Macrophages", Advanced Functional Materials, 2021, 31, 2008698. 
61. 
    
62. 
    
63. "Nanotechnology for Targeted Identification and Eradication of Bacteria: Opportunities and Challenges", Advanced Science, 2021, 8, 2007949. 
64. 
    
65. 
    
66. “Dynamic Ligand Screening by Magnetic Nanoassembly Modulates Stem Cell Differentiation", Advanced Materials, 2021, 34, 2105460.

• 
  
• 
  
• "Conformation- and phosphorylation-dependent electron tunnelling across self-assembled monolayers of tau peptides", Journal of Colloid and Interface Science, 2021, 606, 2038-2050. 
• 
  
• 
  
• "Remote Control of Time-Regulated Stretching of Ligand-Presenting Nanocoils In Situ Regulates the Cyclic Adhesion and Differentiation of Stem Cells", Advanced Materials, 2021, 33, 2008353.
• 
  
• 
  
• "Nkx6.1 promotes neurogenesis and attenuates glial scar formation in the injured spinal cord", Experimental Neurology, 2021, https://doi.org/10.1016/j.expneurol.2021.113826
• 
  
• 
  
• "Gsx1 Promotes Locomotor Functional Recovery After Spinal Cord Injury", Molecular Therapy, 2021, 29, 8-1.
• 
  
• 
  
• "Immunoregulation of Macrophages by Controlling Winding and Unwinding of Nanohelical Ligands", Advanced Functional Materials, 2021, https://doi.org/10.1002/adfm.202103409
• 
  
• 
  
• “Restoring endogenous repair mechanisms to heal chronic wounds with a multi-functional wound dressing”, Molecular Pharmaceutics, 2021, 18, 3171-3180. 

지도교수: 이기범

(2024년 현재)

Post Docs / Visiting Scholars: Dr. Euiyeon Lee, Dr. Hye Kyu Choi, Dr. Teobaldo Molina, Dr. Wankyu Ko, Dr. Mehdi Kamali, Dr. Kim-Phuong Le, Dr. Hongwon Kim, Dr. MinKyu Shin

Graduate students: Yannan Hou, Brandon Conklin, Meizi Chen, Callan McLoughlin, Joshua Stein, Sarah Nevins, Li Ling Goldston, Hyunjun Jang, Diana Hadid, Annelisse

Undergraduate Students: Aisha Mansoor, Margaret Lin, Lancy Zheng, Rohan Kulbe, Kevin Trinh, Divyasri Moulee, Samir Itani

Contact : kblee@rutgers.edu 

Homepage

본 연구실은 화학, 생물학, 공학 분야의 다양한 배경을 가진 학생과 박사후 연구원들로 구성되어 있으며, 구성원들 간의 긴밀한 협업을 통해 나노기술을 기반으로 한 재생의학 응용 연구를 수행하고 있습니다. 본 연구실에서는 다학제적인 접근 방식을 통해 혁신적인 연구를 진행하고 있으며, 이를 통해 재생의학과 나노의학 분야에서의 새로운 돌파구를 마련하고자 합니다.

특히, 본 연구실에서는 졸업 후 또는 연구 활동 이후 미국 진출을 목표로 하는 학생 및 박사후 연구원 분들을 적극 환영하고 있습니다. 본 연구실에서의 연구 경험과 성과는 미국과 한국에서의 학업 및 연구 활동에 큰 도움이 될 것으로 기대됩니다. 또한, 본 연구실에서는 구성원들의 역량 강화와 경력 개발을 위해 다양한 지원을 제공하고 있습니다.

창의적이고 도전적인 마인드를 가진 학생 및 박사후 연구원 분들의 많은 관심과 지원 바랍니다. 본 연구실에서 여러분의 잠재력을 마음껏 발휘하며, 재생의학과 나노의학 분야에서의 혁신을 이끌어나가는 우수한 인재로 성장하시기원하시는 분들은 적극적으로 연락 주셨으면 합니다. 

[진행중인 연구과제]

1) 미 국립보건원 (다수)

2) 뉴저지 암 연구, 척수손상 연구

3) 미 국립과학재단

4) 알츠하이머 협회

[Contact information]

Email: kblee@rutgers.edu

Lab homepage: https://kblee.rutgers.edu/