Xiaorong Lin

Research in Lin laboratory focuses on medical mycology: We study the molecular mechanisms of fungal pathogenesis and microbial communication and development. We also seek to develop novel antifungal treatments and vaccines. We primarily use two diverged fungal pathogens in our investigation: Cryptococcus neoformans and Aspergillus fumigatus. The long-term goal of our research is to seek better approaches for the management of fungal diseases and to advance our knowledge about eukaryotic microbiology.

Cryptococcus neoformans is the causative agent for cryptococcal meningitis. Cryptococcal meningitis is the most common fungal infection of the central nervous system (CNS) and the third most frequent neurological complication in AIDS patients. This disease claims hundreds of thousands of lives annually and is responsible for 15% of deaths in AIDS patients. Human infection is acquired by inhalation of airborne cryptococcal cells from environment and asymptomatic carriage of this fungus is common in the human population. Infection is typically cleared or dormant (latency). When the host immunity is compromised (due to HIV infection or organ transplant), dormant fungal cells can be reactivated and disseminate hematogenously to cause systemic infection, with a propensity to the CNS. We are interested in cryptococcal life cycle and how it contributes to the progression of cryptococcal disease. We are also interested in the molecular mechanisms underlying cryptococcal morphogenesis as morphotype is tightly linked to cryptococcal virulence. For instance, the filamentous form is attenuated in virulence and it promotes host protective immune-responses.  We are exploring the possibility of using the filamentous strains or antigens presented in cryptococcal filaments as vaccine candidates. Investigating the signal transduction pathways that promote cryptococcal filamentation program may provide insights into novel means to mitigate cryptococcal pathogenesis.

Aspergillus fumigatus is the causative agent of Aspergillosis, which varies from an allergic response, aspergillomas to severe invasive aspergillosis.  A. fumigatus is a major threat to bone marrow and solid organ transplant patients worldwide. This fungus grows in the hyphal form and produces asexually by conidiation (the process of generating asexual spores).  A person inhales hundreds or even thousands of A. fumigatus conidia daily. Melanin coated on conidia is critical for fungal survival both in the environment and in the host. Melanins are resistant bio-pigments and also an important secondary metabolite that confers resistance to radiation and other abiotic and biotic stresses. We are interested in understanding the regulation of melanin biosynthesis and cellular trafficking.  In particular, we are focused on the mechanisms that regulate the subcellular compartmentalization of melanization. Compartmentalization of secondary metabolism in membrane-bound organelles is expected to confer several advantages. First, it concentrates multiple enzymes that need to function sequentially to produce these compounds (metabolic channeling). Second, enclosing substrates/precursors together with the enzymes in the same compartment facilitates enzymatic reactions. Third, sequestration of toxic compounds minimizes their potential damage to other cytoplasmic machinery. Lastly, it provides an efficient means to traffic and deliver charged compounds or macro-molecules across the plasma membrane. We are currently investigating the molecular mechanisms underpinning the subcellular regulation of fungal secondary metabolism pathways.

Alumni

Yumeng Fan (former PhD graduate student, currently a postdoc at Chinese CDC)

Fanglin Zheng (former postdoctoral fellow, currently a professor at the First Affiliated Hospital of Nanchang University)

Jianfeng Lin (former PhD graduate student, currently a postdoc at UCLA medical school)

Kenton Hipsher (former MS graduate student, currently a staff scientist at Zymergen)

Bing Zhai (former PhD graduate student, currently a professor at Shenzhen Institute of Synthetic Biology, Chinese Academy of Sciences)

Rachana Gyawali (former PhD graduate student, currently a senior staff scientist at North Carolina State Lab of Public Health)

Linqi Wang (former postdoctoral fellow, currently a professor at Institute of Microbiology, Chinese Academy of Sciences)

Nadia Chacko (former postdoctoral fellow, currently a scientist at LifeMine Therapeutics)

Xiuyun Tian (former postdoctoral fellow, currently a staff scientist at Institute of Microbiology, Chinese Academy of Sciences)

Xinping Xu (former postdoctoral fellow, currently a professor at the First Affiliated Hospital of Nanchang University)

Yunfang Meng (former visiting MD/PhD student, currently a physician at Jianan Hospital)

Srijana Upadhyay (former research associate, currently a research associate at Texas A&M Vet school)